small molecules

2026-06-01 | Effectiveness of once-daily orodispersible budesonide 1 mg as maintenance therapy in eosinophilic oesophagitis: a pragmatic real-world cohort study

Aims Eosinophilic oesophagitis (EoE) is a chronic immune-mediated oesophageal disease requiring long-term anti-inflammatory therapy [ 1 ]. Budesonide orodispersible tablets (BOT) are licensed for induction and maintenance treatment [ 2 ], although real-world induction outcomes are more variable. The population-based DanEoE cohort reported 48% histological, 57% clinical and 39% combined remission after induction [ 3 ], illustrating the challenge of achieving stable disease control outside trial conditions. In the UK, maintenance prescribing policies vary geographically, leading many patients to choose a once-daily 1 mg regimen after induction to avoid treatment breaks. However, evidence for the effectiveness of this regimen is limited. This study aims to evaluate the real-world effectiveness of once-daily orodispersible budesonide 1 mg as maintenance therapy in adult EoE patients. Methods We conducted a single-centre prospective observational cohort study, over 25 months (Oct 2023–Nov 2025), of adults with confirmed EoE who achieved histological remission<15 eosinophils / high powered field (phpf) following induction BOT, and chose to take 1 mg once-daily maintenance. Disease activity was assessed using endoscopy and/or capsule sponge test (Endosign) with EREFS scoring, histology (peak eosinophil count phpf). Symptoms were documented using the Dysphagia Symptom Questionnaire (DSQ) and direct symptom enquiry. Primary endpoints were histological and clinico-histological remission. Secondary endpoints included DSQ outcomes and phenotype-based comparisons. Results 30 patients commenced once-daily 1 mg maintenance therapy (median age 46 years, IQR 32–58; 57% male). The median duration of maintenance treatment before reassessment was 17.9 weeks (IQR 12.3–35.6). Of these, 29/30 (96.7%) patients underwent gastroscopy, and 20/30 (66.7%) had same-day capsule sponge sampling; 1/30 (3.3%) had capsule sponge only. Using the highest peak eosinophil count across gastroscopy and capsule sponge, 25/30 (83.3%) were in histological remission and 5/30 (16.7%) had active inflammation. Clinical remission occurred in 26/30 (86.7%) patients. Clinical remission occurred in 26/30 (86.7%). DSQ scores were available for 23/30 (76.7%), of whom 14/23 (60.9%) had a DSQ score of 0. Clinico-histological remission occurred in 23/30 (76.7%). Among the 29 gastroscopy patients, 16/29 (55.2%) had fibrostenotic disease and 12/29 (41.4%) had inflammatory-only disease. Histological remission occurred in 13/16 (81.3%) fibrostenotic patients vs 11/12 (91.7%) inflammatory patients (Fisher p=0.61). Clinical remission occurred in 13/16 (81.3%) vs 11/12 (91.7%) (p=0.61). Clinico-histological remission occurred in 11/16 (68.8%) vs 10/12 (83.3%) (p=0.66). Median treatment duration did not differ significantly between phenotypes (p=0.35). Conclusions In this real-world cohort once-daily 1mg BOT maintained remission with similar or better efficacy to reported series using twice daily dosing. These findings support dose de-escalation after induction therapy to a once daily 1mg regime which may be easier to implement. They also demonstrate the previously reported use of capsule sponge sampling in monitoring EoE. Larger studies with extended follow-up are needed to confirm these findings but this study supports current pragmatic clinical practice. Additionally, once daily treatment may also improve compliance and be more financially acceptable. Publication History Article published online: 05 June 2026 © 2026. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Open article ↗

2025-10-01 | S6038 Beyond the Gut: “Fighting With the Red Soldiers”

Introduction: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated conditions characterized by eosinophilic infiltration of the gastrointestinal (GI) tract in the absence of known secondary causes such as infections, medications, or systemic disorders. We present an interesting case from India of eosinophilic gastroenteritis (EoGE) with serosal involvement & eosinophilic ascites (EA) in a patient with autoimmune thyroiditis & vitiligo, highlighting the importance of early recognition & diagnosis. Case Description/Methods: A 37-year-old woman presented with poor appetite, gastroesophageal reflux disease, intermittent dysphagia & vomiting. She suffered from hypothyroidism, vitiligo & atypical interstitial pneumonia. She had been using herbal medication for vitiligo. Physical examination revealed a tender abdomen & ascites. Laboratory evaluation showed a leukocyte count 19,900/mm³, with 54% eosinophils. Parasitic diseases & malignancy were tested negative. Abdominal imaging revealed moderate ascites, thickening of the stomach & small bowel walls & a near-complete pyloro-duodenal obstruction. Ascitic fluid analysis showed high protein content and 80% eosinophils. Bone marrow biopsy confirmed eosinophilia without malignancy. Endoscopy revealed mild duodenal edema & rectal ulcers. Biopsies demonstrated moderate-to-dense eosinophilic infiltration & mucosal changes throughout the GI tract, consistent with eosinophilic gastroenteritis. The patient was treated with budesonide & a proton pump inhibitor (PPI), resulting in rapid symptom relief. Azathioprine was added for maintenance therapy & steroids were tapered off. On follow-up, she remained symptom free & ascites had resolved. Three years later, she presented with dysphagia. Endoscopy revealed esophageal rings in the distal esophagus & duodenal erosions. Biopsies showed chronic non-specific inflammation. The laboratory tests were normal. Her symptoms improved with a short course of corticosteroids & dietary modifications. Discussion: This case underscores the importance of maintaining a high index of suspicion in patients with unexplained GI symptoms, peripheral eosinophilia & eosinophilic ascitic fluid. A multidisciplinary approach including imaging, endoscopy & histopathology is crucial for timely diagnosis, especially in regions like India, where the pattern of disease is shifting from infectious to autoimmune etiologies. Individualized immunosuppressive strategies & long-term surveillance are crucial to manage chronic and relapsing course of EoGE.

Open article ↗

2025-10-01 | S4464 Bloody Eosinophils! Upper Gastrointestinal Bleed and Ulceration Unresponsive to Proton Pump Inhibitors in a Young Man With Eosinophilic Gastrointestinal Disease

Introduction: Eosinophilic gastrointestinal disease (EGID) is characterized by eosinophil infiltration in the gastrointestinal tract without secondary causes. Eosinophilic gastroenteritis, a subtype affecting the stomach and small intestine, predominantly affects adults aged 30-50, with a prevalence of 22-28 cases per 100,000 persons in the U.S. Although commonly linked to allergic conditions, this article presents a rare and significant case of eosinophilic gastroenteritis manifesting as upper gastrointestinal bleeding (UGIB) in a 35-year-old man without typical atopic disorders, underscoring the importance of considering EGID in the differential diagnosis of acute UGIB. Prompt recognition can prevent complications and significantly improve patient outcomes. Case Description/Methods: A 35-year-old man with a history of gastric ulcers, hypertension, and pre-exposure prophylaxis presented with hematemesis, coffee-ground emesis, and melena, accompanied by fatigue, jaw pain, and intermittent reflux symptoms. His medications included pre-exposure prophylaxis, amlodipine, citalopram, and naproxen. Past procedures included an esophagogastroduodenoscopy (EGD) in 2006 for a gastric ulcer and normal colonoscopies in 2009 and 2010. Initial laboratory findings demonstrated hemoglobin of 14.0 g/dL and leukocytosis. EGD showed gastric and duodenal ulcers with a visible vessel treated by cautery; biopsies were deferred due to active bleeding. The patient had no further bleeding episodes and was discharged with hemoglobin of 9.4 g/dL. Eight weeks later, a repeat EGD revealed non-bleeding ulcers, and biopsies confirmed eosinophilic esophagitis and gastritis. Treatment consisted of fluticasone and high-dose proton pump inhibitors (PPIs). Discussion: This case emphasizes a rare presentation of EGID as UGIB and highlights the clinical necessity of considering EGID in patients with unexplained gastric and duodenal ulcers. Diagnosis typically relies on histological evidence of elevated eosinophils (>30 eosinophils/HPF in the stomach, >52 in the duodenum). Although peripheral eosinophilia occurs in approximately 70% of cases, diagnosis can be complicated when active bleeding prevents biopsies. Pathogenesis involves IgE-dependent and Th2 cell-mediated allergic responses resulting in eosinophil infiltration and subsequent tissue damage. Standard treatments include corticosteroids and PPIs, with PPIs notably effective in reducing eosinophil-driven inflammation. This case reinforces the critical importance of early recognition and management of EGID to optimize patient outcomes.

Open article ↗

2025-10-01 | S4554 Beyond the Bloodstream: Gastrointestinal Involvement in Idiopathic Hyper-Eosinophilic Syndrome

Introduction: Hypereosinophilic Syndrome (HES) is a rare group of disorders characterized by prolonged eosinophilia, with tissue damage. We present here a rare case of idiopathic hypereosinophilic syndrome with primary gastrointestinal involvement. Case Description/Methods: The patient is a 25-year-old woman, history of asthma and multiple food allergies, with a 2-week history of intermittent right-sided abdominal pain, worsened by food, associated with nausea, vomiting, and intermittent diarrhea. Her vital signs were normal, she appeared ill with dry mucous membranes and diffuse abdominal tenderness. Laboratory tests elevated WBC 44, with 69% eosinophils, Hgb of 14.5, and platelet 258. A computed tomography scan of the abdomen and pelvis showed dilated, fluid-filled loops of the small bowel, multiple thickened small bowel loops, ascites, and small bilateral pleural effusions. Despite empiric treatment with albendazole initiated by the infectious disease team, her eosinophil count continued to rise. Stool testing was negative. Peripheral smear showed severe eosinophilia with mild neutrophilia. Esophagogastroduodenoscopy: Mildly inflamed stomach with a normal duodenum. with increased tissue eosinophilia involving the lamina propria. Colonoscopy: inflamed, and nodular mucosa in the colon and terminal ileum. with increased lamina propria eosinophils throughout. Bone marrow biopsy: negative. Given that the absolute neutrophil count was 30, the patient met the criteria for idiopathic hypereosinophilic syndrome and was started on solumedrol 60 mg intravenous 3 times a day. She exhibited a dramatic decrease in white blood cell count from 42 (79% eosinophils) in the morning to 17 (65.8% eosinophils) by the afternoon, and further to 11 (2.4% eosinophils) the following day, with marked improvement in her symptoms. The patient was then transitioned to a tapering dose of steroids, along with an antihistamine, an H2 blocker, and an anti-IL-5 antibody. Discussion: Hypereosinophilic syndrome (HES) is diagnosed when hypereosinophilia is accompanied by tissue damage and other potential causes of eosinophilia or tissue damage are excluded. HES with primary gastrointestinal eosinophilic diseases (EGIDs) is rare, with only 34 reported cases. We report a 25-year-old woman with idiopathic IHES and multifocal gastrointestinal involvement. There are no formal guidelines for managing EGIDs, current recommendations include dietary modifications, glucocorticoids, In our case, solumedrol 60 mg intravenous 3 times a day led to significant and rapid improvement in both laboratory markers and clinical symptoms.

Open article ↗

2025-08-01 | OC66 Eosinophilic colitis in children with neuro-disability: a tertiary center’s experience of four cases

Eosinophilic colitis (EoC) is a subtype of eosinophilic gastrointestinal disorders (EGID) beyond eosinophilic esophagitis (EoE) which has been recently updated as a nomenclature.1 It describes chronic inflammatory disorders of the gastrointestinal (GI) tract characterized clinically by the GI symptoms and histologically by eosinophilic inflammation, in the absence of a secondary cause. EoC is the least understood of the non-EoE. EGIDs, as its clinical presentation can be confused with IBD (inflammatory bowel disease) such as ulcerative colitis or Crohn disease.2 We report 4 patients who were referred to us with chronic per rectal bleeding, abdominal pain and diarrhea and raised faecal calprotectin. The median age was 11 years. They all had neuro-disability with severe development delay, non-verbal and were gastrostomy fed. Two of them had underlying syndromes. All of them were on hypoallergenic feeds with no allergic history. There were no drug associations found. On upper endoscopy and colonoscopy, there were patchy areas of submucosal hemorrhages which were mainly identified in the proximal colon. Macroscopically (figure 1), they have not been described in EoC but correlated histologically with the suggested threshold peak eosinophil counts of EoC. One had associated EoE but the remaining did not have any upper GI changes. One of them was eventually diagnosed with Crohn’s disease and subsequently passed away due to other, non GI related health issues. Rest were treated with sulfasalazine and are currently symptom free. We concluded that faecal calprotectin can be elevated in children with EoC.3 The macroscopic findings at colonoscopy were unique to these children with neuro-disability. They were all on anti-epileptic medications but none of them are reported to be associated with EoC as an adverse effect. The presence of thresh-hold increased eosinophils in the colonic mucosa requires consideration for a secondary cause, especially IBD as EoC is rare and remains a diagnosis of exclusion. More data to ascertain if EGID is more common in neuro-disabled children is required since there is a lack of published data about EGID. Papadopoulou A, Amil-Dias J, Auth MK-H, Chehade M, Collins MH, Gupta SK, Gutiérrez-Junquera C, Orel R, Vieira MC, Zevit N, Atkins D, Bredenoord AJ, Carneiro F, Dellon ES, Gonsalves N, Menard-Katcher C, Koletzko S, Liacouras C, Marderfeld L, Oliva S, Ohtsuka Y, Rothenberg ME, Strauman A, Thapar N, Yang G-Y, Furuta GT. Joint ESPGHAN/NASPGHAN guidelines on childhood eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2024;78:122–152. https://doi.org/10.1097/MPG.0000000000003877 Al-Haddad S, Riddell RH. The role of eosinophils in inflammatorybowel disease. Gut. 2005;54:1674–5. Rohani P, Beheshti NR, Alimadadi H, et al. Association of fecal calprotectin level with eosinophilic gastrointestinal disease in Iranian pediatrics. Allergy Asthma Clin Immunol. 2022;18:86. https://doi.org/10.1186/s13223-022-00728-5

Open article ↗

antibodies

2026-06-01 | OC63 Dupilumab in highly refractory eosinophilic esophagitis in children

Eosinophilic Oesophagitis (EOE) has several recognised conventional treatments. More recently dupilumab (anti IL-4 and IL-13) has been shown to an effective treatment for EoE for children and adults. There is a paucity of data on the efficacy of dupilumab in the treatment of refractory EoE or with associated non-EoE EGID. In this study we aimed to identify indication and efficacy of dupilumab in multi-treatment refractory EoE in children. We conducted a retrospective review of patients with eosinophilic oesophagitis (EoE) refractory to conventional therapies who received dupilumab for a minimum of three months at our specialized centre. Clinical (PEESS vers. 2) and histological responses were evaluated at 3 and 6 months following treatment initiation. Four male patients (mean age 13.5 years) were included; three had isolated eosinophilic oesophagitis (EoE), and one had concomitant eosinophilic colitis. Abdominal pain was the predominant symptom (100%), followed by dysphagia, vomiting, and regurgitation (75%), and food impaction (50%). The primary indication for initiating dupilumab was refractory disease despite multiple conventional treatments, including corticosteroids. Two patients (50%) developed adrenal insufficiency secondary to prolonged corticosteroid use. None of the patients achieved clinical or histological remission prior to starting dupilumab. Following dupilumab therapy, two patients (50%) demonstrated both clinical improvement and histological remission at 3 and 6 months respectively. One patient (25%) showed partial clinical response without histological remission within six months of treatment, leading to cessation of steroids and initiation of an elemental diet. Dupilumab is licensed by not remunerated in the UK for children over the age of 1. Due to the requirement for local funding, its use is restricted. Approval has been gained at our site for those who have displayed refractory EoE or who have significant side-effects to treatment. This small study shows that dupilumab can be an effective treatment for this cohort and should be considered by funding bodies for use more widely in the UK.

Open article ↗

2026-05-18 | Presentation and treatment of eosinophilic gastroenteritis in Busan and Gyeongnam, Korea: A multicenter study

BACKGROUND Eosinophilic gastroenteritis (EGE) is a relatively rare disease characterized by eosinophilic infiltration of the gastrointestinal wall. Limited data are available regarding the clinical characteristics, treatment patterns, and outcomes of patients with EGE in Korea. AIM To investigate the clinical features, endoscopic findings, treatments, outcomes, and treatment response and relapse predictors in the abovementioned population. METHODS We retrospectively reviewed the medical records of 73 patients with histologically confirmed EGE in Busan and Gyeongnam, Korea, from 2010 to 2023. Clinical, endoscopic, laboratory, and treatment-related data were collected. RESULTS The median patient age was 52 years, and 50.7% of the patients were female. Of the patients, 35 had enterocolitis, 34 had gastroduodenitis, and four had gastroenterocolitis. Endoscopic abnormalities were observed in 82.2% of the patients. Proton pump inhibitors were prescribed primarily for gastroduodenitis, whereas corticosteroids were prescribed more frequently for enterocolitis and gastroenterocolitis. The clinical response rates were high for all groups (75.0%-90.3%); however, relapse occurred more frequently in patients with enterocolitis (43.3%). Male sex was associated with clinical response, although this association should be interpreted with caution; no significant predictors of relapse were identified. CONCLUSION Patients with EGE exhibit diverse clinical characteristics and treatment patterns. While the clinical response to primary treatment is relatively high, relapse is more common in patients with enterocolitis, indicating the need for location-based strategies and close follow-up.

Open article ↗

2026-04-13 | Dupilumab as a rescue therapy for steroid-dependent eosinophilic gastritis in a child unresponsive to elimination diet: a case report

Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, rare and heterogeneous disorders characterized by eosinophilic infiltration of gastrointestinal tract, resulting in gastrointestinal dysfunction. Although standard-of-care therapeutic strategies for eosinophilic esophagitis (EoE) are well-defined, limited evidence on successful treatment of eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) in children is available. While dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, is currently approved in children with EoE, only anecdotal studies assessed its effects in children with non-EoE-EGIDs. Case presentation: This case report describes the successful use of dupilumab as a rescue therapy for a 14-year-old male with concurrent EoE and Eosinophilic Gastritis (EoG), unresponsive to dietetic approach. Despite initial responsiveness to steroid treatments, the patient experienced challenges in tapering off oral steroids without relapse. The administration of dupilumab at a dosage of 300 mg once a week led to clinical, endoscopic, and histological improvement after three months of therapy, highlighting its efficacy as a well-tolerated treatment option. Conclusions: The successful use of dupilumab as a single-therapy therapy in a steroid-dependent child, who did not respond to dietary interventions, highlights its potential in mitigating the development of steroid-related side effects. This report underscores the need for further research and clinical trials to deepen our understanding and optimize the use of dupilumab and other monoclonal antibodies in managing pediatric EGIDs, establishing a basis for the future development of treatment guidelines and protocols.

Open article ↗

2026-04-13 | Eosinophilic and mastocytic gastrointestinal diseases: current knowledge and controversy in histopathologic diagnosis.

Eosinophilic and mastocytic gastrointestinal (GI) diseases represent a spectrum of immune-mediated inflammatory disorders characterized by abnormal accumulation of eosinophils or mast cells in the GI tract. This review summarizes current knowledge on epidemiology, pathogenesis, histopathologic features, diagnostic challenges, and ongoing controversies across three major domains: eosinophilic esophagitis (EoE), non-EoE eosinophilic gastrointestinal diseases (EGID), and mastocytic GI diseases. Although these entities are increasingly recognized in clinical practice, their diagnosis remains challenging because clinical manifestations are often nonspecific and overlap with other inflammatory and functional GI disorders. Consequently, substantial uncertainties persist regarding diagnostic criteria and clinical relevance of certain histologic patterns. For non-EoE EGIDs, histologic diagnosis is particularly complicated by wide regional variation in normal eosinophil densities, the lack of universally accepted diagnostic cutoffs in adults, and limited correlation between tissue eosinophil burden and symptom severity. In mastocytic GI diseases, additional challenges include distinguishing reactive mast cell hyperplasia from clonal mastocytosis and interpreting proposed entities such as mastocytic enterocolitis, whose clinical significance remains controversial. Given these limitations, histopathologic evaluation of GI biopsies plays a central role in disease recognition and classification. This review emphasizes practical aspects of tissue interpretation, including site-specific reference ranges, proposed diagnostic thresholds, characteristic morphologic patterns, ancillary immunohistochemical and molecular studies, and common interpretive pitfalls encountered in routine practice. Recognizing these diseases ultimately requires careful clinicopathologic correlation, integrating histologic findings with clinical, endoscopic, and molecular data. Improved standardization of diagnostic criteria and clearer definition of histologic thresholds remain critical unmet needs for both pathologists and clinicians managing these complex disorders.

Open article ↗

2026-03-26 | From esophagus to colon: A narrative review of eosinophilic gastrointestinal disorders.

Eosinophilic gastrointestinal disorders (EGID) are a heterogeneous group of chronic diseases characterized by excessive infiltration of eosinophils in the gastrointestinal tract in the absence of identifiable secondary causes. Primary EGID includes eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis. The purpose of this review is to provide a concise overview of the current understanding and management of EGID. The published data were extracted by a comprehensive literature search in PubMed/MEDLINE with keywords related to EGID. The retrieved data were analyzed and synthesized into a narrative review emphasizing clinical features, evaluation, and treatment strategies. A brief outline of the etiopathogenesis of the disease was also derived from the published literature. EGID, especially esophagitis, has demonstrated an increasing global prevalence, more frequent in men and those with other atopic conditions. The etiology of EGID remains poorly understood, though allergic mechanisms are heavily implicated. Sensitization to foods or aeroallergens is common, yet only a minority experiences food-induced anaphylaxis, suggesting distinct non-IgE-mediated pathways in disease pathogenesis. Genetic factors and dysregulation in gene expression related to eosinophil recruitment, notably eotaxin-3, are implicated as well. The clinical manifestations vary according to the site of gastrointestinal tract involvement. The diagnosis relies on endoscopic biopsies to reveal the tissue eosinophilia. The treatment strategies include dietary modification or elimination diets, steroids and other anti-allergic medications, proton pump inhibitors, and monoclonal antibodies targeting eosinophils or key inflammatory cytokines. Therapeutic endoscopic procedures might benefit patients with strictures, particularly those involving esophagus.

Open article ↗

cell therapies

2024-08-13 | Balancing immune responses: regulatory cells in eosinophilic gastrointestinal disorders.

Eosinophilic gastrointestinal disorders (EGIDs) are a group of conditions characterized by an abnormal accumulation of eosinophils in the gastrointestinal tract, leading to inflammation and tissue damage. Regulatory cells are a subset of immune cells that are crucial in maintaining the balance of the immune system and preventing the occurrence of autoimmune diseases. In EGIDs, regulatory cells are believed to play a key role in controlling the immune response and overseeing the growth and activation of eosinophils in the gastrointestinal tract. There is evidence indicating that regulatory T cells (Tregs) and regulatory eosinophils may play a role in suppressing the inflammatory response in EGIDs. Regulatory eosinophils are a subgroup of eosinophils that possess an anti-inflammatory role. Recent studies have shown that enhancing the number or effectiveness of regulatory eosinophils can reduce the severity of EGIDs. Regulatory eosinophils dampen inflammation through their regulatory mediators, such as galectin-10 and growth factor beta (TGF-β), which promote Treg expansion and inhibit effector T cell function. Further research on regulatory cells in EGIDs may have significant implications for the advancement of novel therapies for these uncommon and intricate disorders. The aim of this review is to provide complete view of the immune responses connected to EGIDs, examine the regulatory cells that control these responses, and evaluate their potential as therapeutic targets for EGID treatment.

Open article ↗

2015-09-05 | Elements Involved In Promoting Eosinophilic Gastrointestinal Disorders

Eosinophilic gastrointestinal disorders (EGID) are food allergen-induced allergic gastrointestinal disorders, characterized by accumulation of highly induced eosinophils in different segments of gastrointestinal tract along with eosinophil microabssess and extracellular eosinophilic granules in the epithelial layer. EGID are both IgE- and cell-mediated group of diseases that include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE) and eosinophilic colitis (EC). Despite the increased incidences and considerable progress made in understanding EGID pathogenesis. The mechanism is still not well understood. It has been shown that IL-4, IL-5, IL-13, IL-15, IL-18, eotaxin-1, eotaxin-2 and eotaxin-3 play a critical role in EGID pathogenesis. Currently, the only criterion for diagnosing EoE, EGE and EC are repetitive endoscopic and histopathological evaluation of biopsies along with other clinical characteristics/manifestations. Antigen elimination and corticosteroid therapies are the most effective therapies currently in practice for the treatment of EGID. The cytokines (anti-IL-5 and anti-IL-13) therapy trials were not very successful in case of EoE. Most recently, a clinical trial using anti-IL-13 reported only 60% reduced esophageal eosinophilia without achieving primary endpoint. This clinical finding is not surprising and is in accordance with our earlier report indicating that IL-13 is not critical in the initiation of EoE. Notably, EGID still has no reliable noninvasive diagnostic biomarkers. Hence, there is a great necessity to identify novel noninvasive diagnostic biomarkers that can easily diagnose EGID and provide an effective therapy. Now, the attention is required to target cell types like iNKT cells that produce eosinophil active cytokines and is found induced in the pathogenesis of both experimental and human EoE. iNKT cell neutralization is shown to protect allergen-induced EoE in experimental model. In this review, we have discussed the key elements that are critical in the disease initiation, progression, pathogenesis and important for future diagnostic and therapeutic interventions for EGID.

Open article ↗

gene therapies

2023-08-24 | Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients

Introduction Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development. Methods We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity. Results Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE ( CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7 ). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports. Discussion Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC , that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.

Open article ↗

2021-05-12 | Pancreaticoduodenectomy for stricturing primary eosinophilic duodenitis.

A 59-year-old woman was referred to a specialist gastroenterologist following a year of intermittent abdominal bloating and worsening reflux. In the month prior to referral, the patient developed intermittent large volume vomiting consisting of bile-stained undigested food. This was accompanied by a 10 kg weight loss. Imaging and endoscopic investigations showed a circumferential thickening of the second part of the duodenum. Biopsy showed non-specific inflammatory changes with marked eosinophilic infiltrates. A pancreaticoduodenectomy was performed. Histopathological analysis of the resection sample showed primary eosinophilic duodenitis with no evidence of malignancy. Immunological testing was only positive for coeliac disease and an infectious cause was never identified. The patient's symptoms resolved following the surgery and she was discharged from surgical follow-up after 8 years of no further symptoms.

Open article ↗

other

2024-09-25 | Eosinophilic gastrointestinal disorders and the role for the epithelium in pathogenesis and treatment.

This review aims to provide an overview of the current understanding of eosinophilic gastrointestinal disorders (EGIDs) and the role of the epithelium in influencing disease pathogenesis to inform and devise future therapeutic strategies. Changes in epithelial cell structure, functions, and integrity are observed in EGIDs. In eosinophilic esophagitis (EoE), the esophageal epithelium has been shown to play key roles in perpetuating the inflammatory response in EoE through the expression of pro-inflammatory cytokines and immunological cell-surface proteins. Similar mechanisms appear to exist in the other EGIDs, including eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Because of the increasing rarity of each non-EoE EGID, research focusing on how the epithelium is modulating disease in each lower gastrointestinal compartment is still in its rudimentary stages. While there has been significant progress in understanding the role of the epithelium in EoE, further research is needed to obtain a better understanding of the mechanisms mediating epithelial-immune crosstalk in non-EoE EGIDs. Using EoE-epithelial cell research to inform future EGID investigations could lead to the development of new therapeutic interventions, such as targeted therapies to restore epithelial barrier function and reduce inflammation, to improve rare disease-patient quality of life.

Open article ↗

2023-06-08 | MicroRNA dysregulation and therapeutic opportunities in esophageal diseases.

MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation. Among this includes the uncovered potential of miRNAs in overall esophageal disease with a focus on the clinicopathologic allergic disease eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and the tumorigenic continuum from Barrett's esophagus (BE) toward esophageal adenocarcinoma (EAC). Although these pathologies are distinct from one another, they share pathophysiological elements such as an intense inflammatory milieu, esophageal dysfunction, and as presented in this review, an overlap in miRNA expression which contributes to overall esophageal disease. The overlap in the dysregulated miRNA transcriptome of these pathologies highlights the key role miRNAs play in contributing to esophageal disease progression. Owing to this notable dysregulation, there is an attractive utility for miRNAs as diagnostic and prognostic biomarkers in esophageal diseases that already require invasive endoscopies and biopsy retrieval. In this review miRNAs within EoE, GERD, BE, EAC, and esophageal achalasia are discussed, as well as reviewing a core set of miRNAs shared in the disease progression among some of these pathologies, along with the potential utility of targeting miRNAs as therapeutic options in overall esophageal disease.

Open article ↗

2022-04-26 | Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study.

Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

Open article ↗