Data on the incidence of Eosinophilic gastrointestinal disease (EGID) distal to the esophagus are scarce. This study aimed to examine the incidence of non-eosinophilic esophagitis (EoE) EGID in Sweden, as well as its three entities; eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC).

We performed a nationwide population-based cohort study of individuals with incident biopsy-confirmed non-EoE EGID in Sweden from 1990 to 2015. Age-standardized and age-specific incidence rates (IRs) were calculated.

We identified 1882 individuals with incident non-EoE EGID. Females constituted 58% and the mean age at diagnosis was 45 years. EoC was the most common subtype (62%). From 1990 to 2015, the mean age-standardized IR was approximately 0.8 per 100,000 person-years (IR = 0.79; 95%CI = 0.64-0.93), but with higher IRs in recent years (2013-2015: IR = 1.51; 95%CI = 1.09-1.93). The incidence increased especially during the 1990s, with a 27% annual increase before 2000, compared to a 3% annual increase thereafter. The incidence rate ratio (IRR) between females and males was 1.38 (95%CI = 1.26-1.51), but no evidence was found to suggest that the IRR varied across calendar periods or by age. The lifetime risk of diagnosed non-EoE EGID was 0.08% (1 in 1250) in females and 0.06% (1 in 1667) in males.

The incidence of non-EoE EGID in Sweden increased between 1990 and 2015. This may reflect a higher disease awareness in recent years.

It is unknown whether concomitant esophageal involvement or anatomic location of eosinophilic infiltration affects the natural history of eosinophilic gastrointestinal disease (EGID).

A retrospective cohort study was performed using the University of North Carolina EGID Clinicopathologic Database. Patients were adults and children with a prior EGID diagnosis based on clinicopathologic features. Demographics, clinical characteristics, treatment information, and procedural data were extracted from medical records. Clinical course and flare history were characterized.

Among 97 patients, 43% had EGID + esophageal involvement and 57% had EGID only. Patients with esophageal involvement had a longer diagnostic delay preceding diagnosis (36.6 vs 11.6 months, P = 0.001), more dysphagia (50% vs 18%; P = 0.001), required more chronic therapy (77% vs 52%, P = 0.016), and exhibited more progressive disease (25% vs 6%, P = 0.027). A continuous disease course was most common in eosinophilic gastritis (78%) while patients with eosinophilic gastritis + eosinophilic enteritis (29%) and eosinophilic enteritis + eosinophilic colitis (50%) had the highest proportion of progressive and relapsing disease, respectively ( P = 0.045). A continuous disease course occurred more frequently in children (71%, P = 0.03) and those with single organ involvement (65%), whereas adults had more relapsing (39%) or progressive disease (18%).

EGIDs with and without esophageal involvement display many similarities, although patients with esophageal involvement more frequently had dysphagia, had progressive disease courses, and required more chronic therapy. Location of involvement and age of onset affected the natural history with higher proportions of relapsing or progressive disease seen in adults and patients with small bowel or multiorgan involvement while a continuous disease course was more common in children and patients with gastric-only involvement.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

Isolated eosinophilic gastroenteritis (EGE) of the second part of the duodenum is rare. We herein report a case of EGE limited to the second part of the duodenum that caused circumferential stenosis due to massive wall thickening. A boring biopsy was useful to verify the accumulation of eosinophils. Induction of remission by prednisolone was accompanied by a marked reduction in the mRNA expression of interleukin-6, C-C motif chemokine ligand 17 (CCL17), and CCL26 without any reduction in prototypical EGE-associated T helper type 2 cytokines (IL-5, IL-13). Thus, the enhanced expression of IL-6, CCL17, and CCL26 might be involved in the development of EGE in this case.

Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE.

Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records.

One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils.

The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.

Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil-predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia.

To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non-EoE EGIDs, and discuss key remaining knowledge gaps.

We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta-analyses.

Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non-EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies.

Unmet needs for research are dramatically different for EoE and non-EoE EGIDs. In EoE, non-invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non-EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders.

Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse.

To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.

This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS).

EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003).

In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs.

The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment.

The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed.

Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Eosinophilic enteritis (EoN), a subtype of eosinophilic gastrointestinal disease, is a rare and complicated inflammatory condition affecting the small intestine. This case report discusses a 42-year-old patient who presented with acute gastrointestinal symptoms including diarrhea, nausea, and vomiting. Initial laboratory investigations revealed leukocytosis, peripheral eosinophilia, and distinctive imaging findings, prompting further evaluation. Endoscopic evaluation revealed extensive mucosal lesions in the small intestine, with subsequent biopsies confirming eosinophilic infiltration, ultimately leading to the diagnosis of chronic enteritis, probably of an eosinophilic nature. The case highlights the complex differential diagnostic process involved in identifying EoN, which requires a comprehensive understanding of all the clinical and histopathological features of the disease. The efficacy of budesonide therapy is also discussed in the management of EoN and it was evidenced by our patient's positive response to treatment. This case report contributes significant insights into the understanding and management of EoN, providing essential information for the medical community to facilitate accurate diagnosis and tailored therapeutic interventions for individuals experiencing this complex disorder.

Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically.

We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE.

Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome.

Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject.

An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis.

gov Identifier: NCT03320369.

The epidemiology of eosinophil-associated diseases (EADs) is not yet fully understood. While some studies have been conducted on stand-alone eosinophilic diseases, there is scarce evidence on the degree of overlap among rarer conditions.

The retrospective Real-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study used data from the Optum® Clinformatics® insurance claims database to describe and characterize disease overlap among 11 EADs: allergic bronchopulmonary aspergillosis, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic gastritis/gastroenteritis, eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis, bullous pemphigoid, chronic obstructive pulmonary disorder, chronic spontaneous urticaria, and non-cystic fibrosis bronchiectasis. Patient records with EADs of interest were identified between January 1, 2015, and June 30, 2018.

Overall, 1,326,645 patients were included; 74.4% had 1 EAD, 20.5% had ≥ 2 EADs, and 5.1% had ≥ 3 EADs. Higher rates of disease overlap were associated with older age. Higher blood eosinophil counts were also observed in patients with a greater number of overlapping conditions, suggesting a common role for eosinophilic inflammation in the pathogenesis of multiple diseases. Furthermore, greater disease overlap was associated with higher disease severity in most cohorts.

Results from this study have implications for quantifying unmet needs and can be used to inform treatment guidelines and raise the awareness of eosinophilic inflammation and EAD overlap among healthcare professionals from a range of disease specialties.

Eosinophilic gastrointestinal disorders are a group of rare diseases characterized by the infiltration of eosinophils in the gastrointestinal wall in a greater amount than in homeostatic conditions. 'Non-esophageal eosinophilic gastrointestinal disorders' is the umbrella term for all eosinophilic gastrointestinal disorders outside of the well known eosinophilic esophagitis. This includes eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis. The clinical presentation is atypical and not very different for the three disorders. The depth of infiltration has a bigger influence on the presenting symptoms than the disease location. Although the frequency of diagnosis and research in this subject is increasing over time, non-esophageal eosinophilic disorders are rare and high quality evidence is limited to date. In this narrative review, we provide an overview of the latest insights in the pathophysiology, diagnostic approach and available treatment options. Transcriptome studies have found the pathogenesis to be T helper type 2 driven. Various laboratory findings can be used to trigger raised suspicion and investigation with endoscopy. As the endoscopic appearance of the mucosa is normal in most cases, multiple biopsies in each segment are needed to quantify the amount of eosinophils in the tissue. Eosinophilic cut-offs for diagnosis are a controversial topic and a consensus is still lacking. A recently developed tissue based diagnostic platform which measures differentially expressed genes might be available in the future to classify patients with intermediate eosinophilic tissue levels under the cut-off. For the treatment, corticosteroids are still the cornerstone of treatment but promising research suggests a role of biologicals, such as Lirentelimab (anti-siglec 8) in particular.

Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature.

This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in 2 consensus meetings, and the framework was updated and reassessed in a second Delphi vote, with a 70% threshold set for agreement.

Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but 2 statements. "EGID" was the preferred umbrella term for disorders of gastrointestinal (GI) tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an "Eo" abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term "eosinophilic gastroenteritis" is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas.

This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term, rather than "eosinophilic gastroenteritis," and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.

Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus.

Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden's all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education.

In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04-1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32-2.48, aHR = 1.50; 95%CI = 1.18-1.89, and aHR = 0.99; 95%CI = 0.85-1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05-1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96-1.35). Comparison of EGID individuals with their siblings yielded similar aHRs.

This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers.

Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions of the gastrointestinal tract that are characterized by tissue eosinophilia and end-organ dysfunction or damage. Primary EGIDs are associated with atopy and other allergic conditions, whereas secondary EGIDs are associated with underlying systemic diseases or hypereosinophilic syndrome. Within the spectrum of EGIDs, eosinophilic esophagitis is the most prevalent. Eosinophilic gastroenteritis and eosinophilic colitis are relatively uncommon. Eosinophilic infiltration of the liver, biliary tree, and/or pancreas also can occur and mimic other inflammatory and malignant conditions. Although endoscopic evaluation is the method of choice for eosinophilic esophagitis, radiologic evaluation of the esophagus plays an important role in the assessment of disease severity. CT and MR enterography are the modalities of choice for demonstrating specific forms of eosinophilic gastroenteritis. CT and MRI are important in the detection of abdominal visceral involvement in EGIDs. Diagnosis is often challenging and relies on symptoms, imaging findings, histologic confirmation of tissue eosinophilia, and correlation with peripheral eosinophilia. Imaging is crucial for identifying characteristic organ-specific findings, although imaging findings are not specific. When promptly treated, EGIDs usually have a benign clinical course. However, a delayed diagnosis and associated surgical interventions have been associated with morbidity. Therefore, a radiologist's knowledge of the imaging findings of EGIDs in the appropriate clinical settings may aid in early diagnosis and thereby improve patient care. An overview of the clinical features and imaging findings of EGIDs and the eosinophilic disorders of associated abdominal viscera is provided. Online supplemental material is available for this article. ^©RSNA, 2022.

The prevalence of psychiatric comorbidity in nonesophageal eosinophilic gastrointestinal disorders (EGIDs) has not been studied. We aimed to ascertain the prevalence of psychiatric diagnoses and psychiatric medication use in children, adolescents, and adults with EGIDs and to assess whether psychiatric comorbidity affects clinical presentation.

This was a retrospective cohort study of newly diagnosed patients with a nonesophageal EGID at the University of North Carolina from 2008 to 2020. Psychiatric diagnoses and medications were extracted from medical records. We compared the clinical and demographic features of EGID patients with and without psychiatric diagnoses.

Of 79 patients (mean 23.3 years of age, 53% male, 78% White) with a nonesophageal EGID diagnosis, 40 (51%) were diagnosed with a comorbid psychiatric disease. Anxiety (37%) and depression (28%) were most common. There were also 40 (51%) patients treated medically for a psychiatric diagnosis. Patients with a psychiatric diagnosis were more commonly ≥18 years of age at the time of EGID diagnosis (odds ratio [OR], 3.95, 95% confidence interval [CI], 1.20-13.02) and had endorsed symptoms of nausea (OR, 5.31; 95% CI, 1.33-21.22) and dysphagia (OR, 4.24; 95% CI, 1.18-15.26).

Psychiatric diagnoses were very common in nonesophageal EGID patients with approximately 7 in 10 adults and one-third of children diagnosed. Similar proportions were found for psychiatric medication use. We also found that psychiatric illness may influence age of clinical presentation and symptoms. Providers should assess for concomitant psychiatric comorbidities in EGID patients.

Eosinophilia and related organ damage are extensively studied hot topics among rare disorders. Any addition to the cohort of available case reports of the same will be adding knowledge for better management of this less known entity.

In this article, we describe a 27-year-old Indo-Aryan man who presented with abdominal pain, abdominal distension, and loose stools for variable days. He had splinter hemorrhages in the majority of fingernails. He was diagnosed with predominant eosinophilic gastrointestinal involvement with bowel obstruction and ascites, and was managed with intravenous immunoglobulin. He was subsequently treated with oral low dose steroid therapy and responded completely.

Our experience is evidence that prompt management of this hypereosinophilic lethal gastrointestinal (all three layers) infiltrative disease provides a cure and avoids complications. Splinter nail hemorrhages may be seen in the same disease.

Studies on eosinophilic gastroenteritis have identified broad spectrums of disease. We aimed to characterize subtypes of disease and ascertain outcomes of each group.

This is a retrospective cohort study from a large tertiary medical center including 35 patients diagnosed with eosinophilic gastroenteritis from 2007 to 2018. We defined 2 groups of patients based on clinical and laboratory findings at presentation. Severe disease was defined as having weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis. The remaining patients were labeled as mild disease group. We collected and compared demographic data, clinical features, laboratory findings, an allergy history, and disease course of both cohorts.

Among 35 patients with eosinophilic gastroenteritis, 18 patients met the criteria for severe disease and 17 patients for mild disease. Of the patients with severe eosinophilic gastroenteritis, 6 (38%) had remission without chronic symptoms, whereas 10 (63%) had chronic symptoms requiring chronic medical therapy. Of the mild group, 12 patients (80%) had disease remission without chronic medications. An allergy history was more common in the severe disease group (83%) compared with the mild disease group (45%). Prednisone and open capsule budesonide were the most commonly used treatment medications in both groups.

Patients with eosinophilic gastroenteritis may be characterized into 2 forms. Patients with weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis were associated with a chronic disease course requiring chronic medications.

Eosinophilic enteritis (EE) is an immune-mediated antigen-driven disease that may lead to clinical symptoms and organ dysfunction and characterized by the presence of extensive eosinophilic infiltrates on histopathological examination of the intestinal mucosa.

A 29-year-old man presented with a half-month duration of paroxysmal upper abdominal pain that gradually evolved into continuous pain accompanied by the urge to defecate.

Pathological findings of enteroscopy showed acute and chronic inflammation accompanied by eosinophilic infiltration (>20/ high-power field).

The patient was initially treated with IV infusion of dexamethasone 10 mg per day for 3 days, which was reduced to 7.5 mg per day for 2 days once pain relief was achieved. Upon discharged from our hospital, the patient was prescribed with oral prednisolone 30 mg per day, which was reduced by 5 mg per week for 6 weeks until discontinuation.

The patient was relieved from the pain after receiving dexamethasone for 5 days, and he was maintained on oral prednisolone 30 mg per day upon discharge from the hospital. On the day of discharge, the eosinophil count and derived ratios were normal.

In patients with EE, the dynamic changes of the eosinophil count should be monitored. Clinicians must be aware that not all patients with EE have a history of allergies. In the management and treatment of the disease, multisite biopsies should be carried out if EE is suspected, and EE is responsive to steroid therapy.

Eosinophilic gastroenteritis (EG) is an autoimmune disorder that involves infiltration of eosinophils in the bowel wall of the stomach and/or intestine, resulting in various gastrointestinal symptoms. The majority of cases are diagnosed by findings of increased eosinophils on mucosal biopsies. We describe a rare type of eosinophilic gastroenteritis with eosinophilic infiltration involving only the muscularis propria layer. This elusive diagnosis was made after a full-thickness intestinal wall biopsy. This predominantly muscular type eosinophilic gastroenteritis can cause intestinal obstruction or perforation. Similar to the predominantly mucosal type eosinophilic gastroenteritis, this type of eosinophilic gastroenteritis responds to low-dose or topical corticosteroids.

Gastric and duodenal mucosa may appear normal in eosinophilic gastroenteritis (EGE). Adult gastroenterologists typically biopsy only in the setting of mucosal abnormalities or symptoms, while pediatric providers biopsy all patients. The biopsy yield of EGE has not been adequately evaluated.

To evaluate the biopsy yield of EGE in a pediatric cohort and assess predictors of increased biopsy yield.

We identified patients age 0-18 who underwent upper endoscopy. We recorded endoscopic findings, pathology, demographics, and clinical and laboratory characteristics. We identified EGE cases (>20 eosinophils per high-power field on stomach and/or duodenum biopsy). We compared characteristics between EGE and non-EGE cases, calculated biopsy diagnostic yield, and performed multivariate analysis for predictors of increased biopsy yield.

In 509 patients (55.6% female, mean age 10.3 years, 69.7% white, 58.7% atopic), biopsy diagnostic yield for EGE was 1.2% (6/509) among all subjects, 7.7% (3/39) for those with peripheral eosinophilia (≥500 eos/uL), 9.1% (3/33) for those with hypoalbuminemia (<3.5 g/dL), and 25.0% (3/12) for those with peripheral eosinophilia and hypoalbuminemia. The odds of EGE were 27.8 (95% CI 3.3-231.8) times greater among those with peripheral eosinophilia. The mean total biopsy surface area and number of fragments was similar between patients with and without EGE. The area under the ROC curve for blood eosinophil counts and albumin level for predicting EGE was 0.926.

The biopsy diagnostic yield for EGE is low but increases with peripheral eosinophilia and hypoalbuminemia. Patients with these features should have biopsies obtained, regardless of endoscopic appearance.

Eosinophilic gastritis/gastroenteritis (EG/EGE) are rare eosinophilic infiltrative disorders in children and adults that fall under the umbrella term eosinophilic gastrointestinal disorders (EGIDs). EGIDs also include eosinophilic esophagitis (EoE) and eosinophilic colitis. In this article, we present the current literature regarding the clinical presentation, diagnostic criteria, and management of EG/EGE.

The underlying complex pathophysiology remains unknown, yet hypersensitivity response is a central component. Unlike EoE, standardized diagnostic criteria are lacking but, promising research employing tissue-based and blood-based methods of diagnosis have been reported. Non-EoE EGIDs are more challenging to treat than EoE. More than a third of patients may achieve spontaneous remission. Still, most will require dietary elimination and/or pharmaceutical interventions, mainly corticosteroids, but also biologics (monoclonal antibodies against IL-4, IL-5, TNFα, integrin α4β7, and IgE), mast-cell stabilizers, leukotriene (LT)-receptor antagonists, and antihistamines. Promising research suggests the role of AK002, an anti-siglec antibody, in clinical and histological improvement. Given the rarity and underdiagnosis of EG/EGE, different natural progression compared to EoE, heterogeneous clinical manifestations, and probable normal endoscopic appearance, it is vital to maintain a high suspicion index in atopic patients, obtain at least 5-6 random biopsies from each site for gastro/duodenal eosinophilic infiltrate with the subsequent exclusion of inflammatory, allergic and infectious differential diagnoses to increase the yield of an accurate diagnosis. Corticosteroids remain the mainstay of treatment, often requiring long-term use. Steroid-sparing agents remain experimental. Goals of therapy move beyond clinical remission but lack evidence to support histological remission.

The growing recognition of eosinophilic gastrointestinal disorders has revealed the limitations of current treatment (mainly based on dietary modification and corticosteroids), and include refractoriness, high recurrence rates, and the need for long-term therapy. Research efforts, mainly in eosinophilic esophagitis (EoE), have unveiled essential pathophysiological mechanisms leading to these disorders, which bear some similarities to those of atopic manifestations and are shared by eosinophilic gastroenteritis (EGE) and eosinophilic colitis (EC). Novel targeted therapies, some imported from bronchial asthma and atopic dermatitis, are currently being assessed in EoE. The most promising are monoclonal antibodies, including those targeting interleukin (IL)-13 (cendakimab) and IL-4 (dupilumab), with phase 3 trials currently ongoing. The potential of anti-integrin therapy (vedolizumab) and Siglec-8 blockers (antolimab) in EGE are also promising. Non-biological therapies for eosinophilic gut disorders, which include preventing the activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and chemoattractant receptor expressed on T helper 2 cells (CRTH2) signaling pathways, and other potential targets that deserve investigation in eosinophilic gut disorders, are reviewed.

A 54-year-old Chinese man presented with ascites for 2 weeks. He had a preceding 2-year history of intermittent dysphagia, lethargy and general malaise. Blood investigations revealed leucocytosis with eosinophilia of 26.5%, whereas paracentesis showed turbid fluid with high protein content (45 g/L) and a high white blood cell count of 5580/µL, predominantly eosinophils (90%). An incidental assay of vitamin D showed a very low level of 13.5 ng/mL. No other cause of ascites was found. Gastroscopy was normal except for duodenitis. However, biopsies from lower oesophagus confirmed the presence of eosinophilic infiltration. Following vitamin D replacement, the patient experienced marked improvement in symptoms of dysphagia within 2 weeks and no recurrence of ascites after 3 months. The reason for the patient's vitamin D deficiency remains unclear. The marked improvement in the patient's health indicates a causative role of vitamin D deficiency in causing eosinophilic esophagogastroenteritis and associated eosinophilic ascites.

Eosinophilic gastrointestinal disorders (EGIDs) are a rare group of inflammatory disorders that can occur anywhere along the gastrointestinal tract, from the esophagus to the rectum. In particular, those with malignant or benign tumors are extremely rare.

A 62-year-old man was referred to our hospital with a chief complaint of abdominal fullness. The peripheral white blood cell count was 19,400/µL, and the eosinophil count was 13,300/µL. Abdominal computed tomography showed massive ascites. Cytology of the ascitic fluid showed a large amount of eosinophils and no malignancy. Upper and lower gastrointestinal endoscopies were performed on the suspicion of EGIDs, and colon cancer with no other abnormalities was found. The biopsies of the cancer lesions and non-cancer lesions also showed significant differences in eosinophil counts per high-power field (HPF) between the cancer and non-cancer lesions (median 77.5 [IQR 52-115] vs. 40.5 [35-56]/HPF, P < 0.05). Exploratory laparoscopy showed cloudy massive ascites and thickening of the mesentery. Pathological examination of the mesentery showed a large amount of eosinophils (median 177.5 [IQR 91-227]/HPF) and no malignancy. Based on these findings, it was suspected that the massive ascites due to eosinophilic peritonitis could be associated with colon cancer. Steroid administration resulted in immediate disappearance of the ascites, and laparoscopic left hemicolectomy was safely performed 6 weeks after steroid administration.

This report presented a case of eosinophilic peritonitis that could be related to colon cancer. Exploratory laparoscopy was useful to detect the cause of ascites. The possibility that eosinophilic peritonitis was associated with colon cancer is discussed based on the histopathological findings.

Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis.

In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score.

Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group).

In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).

Eosinophilic gastrointestinal diseases (EGIDs) are defined by marked eosinophilia in the gastrointestinal (GI) tract resulting in a wide variety of GI symptoms. When accompanied by blood hypereosinophilia (HE; absolute eosinophil count ≥1500/mm3), EGID can occur as an isolated GI disorder (hypereosinophilic syndrome [HES]/EGID overlap) or as part of a multisystem hypereosinophilic syndrome (Multisystem HES).

To describe the GI disease of patients categorized as those with HES/EGID overlap versus those with Multisystem HES.

Consecutively enrolled patients on a natural history protocol to study eosinophilia with biopsy-proven EGID involving the esophagus, stomach, small-bowel, and/or colon were evaluated for clinical, histopathologic, and endoscopic features by retrospective chart review.

Among the 56 patients with EGID and HE, 34 were categorized as HES/EGID overlap and 22 as Multisystem HES. Demographics, GI symptoms, and associated comorbidities were similar between the 2 groups. Multisegment GI eosinophilia was present in 20 of 30 (67%) patients who underwent tissue sampling of all 4 GI segments. Tissue eosinophilia in all 4 GI segments was found in 5 of 30 (17%) patients. Dietary therapy was more common in patients with HES/EGID overlap (65% vs 23%, P = .0028). Patients with Multisystem HES were more likely to receive glucocorticoids (100% vs 79%, P = .0349) and nonglucocorticoid systemic therapies (77% vs 38%, P = .0061). One-third (8 of 22) of patients with Multisystem HES presented with isolated GI symptoms before developing extraintestinal manifestations at a median of 1 year (range, 0.25-15 years).

There are striking clinical similarities between patients with Multisystem HES and those with HES/EGID overlap, despite differing treatment approaches. Moreover, Multisystem HES can present with isolated GI involvement. Larger prospective studies are needed to confirm these findings.

Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary eosinophilic infiltrate in the colon wall in symptomatic patients. While the etiology of primary colonic eosinophilia is unknown, several conditions are involved in the pathogenesis of secondary eosinophilic colonic infiltrate (food allergens, parasitic infections, drugs), which have to be excluded in order to correctly diagnose the primary form of the disease. Up to now, EC is lacking of codified guidelines regarding diagnostic criteria (especially eosinophil threshold values) and treatment, thus a correct approach to EC remains very challenging. Imaging, laboratory tests and endoscopy might be helpful in ruling out other mimic conditions, but EC is still a diagnosis of exclusion. Several treatment options are feasible, but most of the evidences are drawn from case reports and small case series, thus limiting their value. We carried out a review of the current literature to evaluate the more appropriate and modern clinical strategy for diagnosis and management of EC.

Introduction: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist.Areas covered: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019.Expert opinion: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.

Eosinophilic enterocolitis is a rare condition included in the spectrum of the eosinophilic gastrointestinal disorders. Diagnosis is based on clinical presentation combined with an increase infiltration of eosinophils in the gastrointestinal tract, in the absence of other secondary causes of eosinophilic infiltration.

We report a case of a 22-year-old male with eosinophilic enterocolitis presenting with malabsorption syndrome (diarrhea, vomiting, weight loss), bowel wall thickening, and ascites. Secondary causes of intestinal eosinophilia were excluded, and diagnosis was established in a timely manner. Treatment plan included a 6-food elimination diet and corticosteroid therapy, with clinical remission after 2 weeks of therapy. The patient remains asymptomatic after 12 months of follow-up, with no relapse.

Eosinophilic gastrointestinal disorders (EGID) are a group of disorders characterized by pathologic eosinophilic infiltration of the esophagus, stomach, small intestine, or colon leading to organ dysfunction and clinical symptoms (J Pediatr Gastroenterol Nutr; Spergel et al., 52: 300-306, 2011). These disorders include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic enteritis (EE), and eosinophilic colitis (EC). Symptoms are dependent not only on the location (organ) as well as extent (layer invasion of the bowel wall). Common symptoms of EoE include dysphagia and food impaction in adults and heartburn, abdominal pain, and vomiting in children. Common symptoms of the other EGIDs include abdominal pain, nausea, vomiting, early satiety, diarrhea, and weight loss. These disorders are considered immune-mediated chronic inflammatory disorders with strong links to food allergen triggers. Treatment strategies focus on either medical or dietary therapy. These options include not only controlling symptoms and bowel inflammation but also on identifying potential food triggers. This chapter will focus on the clinical presentation, pathophysiology, and treatment of these increasingly recognized disorders.

Eosinophilic gastroenteritis (EGE) is a rare idiopathic disease affecting multiple organs (stomach and small intestine) of the digestive tract. It is characterized by eosinophilic infiltration of the bowel wall to a variable depth and symptoms associated with gastrointestinal tract disease. The prevalence of this condition is ranging from 8 and 28 per 100,000. We present a rare presentation of EGE manifesting as upper GI bleeding.  A 28-year-old male with PMH of EGE, duodenal ulcers, and stricture presented to the hospital with the chief complaints of three episodes of dizziness and melena over one day. His home medications included prednisone, montelukast, and pantoprazole. On admission, he was found to be tachycardic (150) while other vital signs were stable. Physical examination revealed cold, pale and clammy skin but was otherwise normal on examination. Initial labs showed hemoglobin (hgb) of 9.3. His hospital course was complicated with 1 episode of large volume hematemesis >1.5 L and brief loss of consciousness for which a code rapid response was called. On day 2, the hgb dropped to 5.7 and the patient received a blood transfusion. Emergent endoscopy (EGD) revealed high-grade duodenal stenosis, severe pyloroduodenal deformity and a duodenal ulcer with the visible vessel. Two clips were deployed blindly. Epinephrine could not be injected due to hard and fibrotic tissue around duodenal stenosis. The Interventional Radiology team was consulted and emergent angiography was done which revealed active bleeding from a branch of the gastric artery. Embolization was done and hemostasis was achieved successfully. He needed 5 units of PRBC transfusion in total. He was treated with pantoprazole twice a day intravenously since admission. For his known duodenal stricture, the surgical team was consulted. No acute surgical intervention was recommended. On discharge, he was sent home with pantoprazole 40 mg twice a day, slow tapering of prednisone and close follow up with gastroenterology, surgery, and primary care doctor within 1 week. The purpose of this case report is to increase awareness about this clinical condition among medical professionals.

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody- mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein-induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. Non-IgE mediated food allergies are being being investigated.

Eosinophilic gastrointestinal disorders are chronic inflammatory diseases in which eosinophils highly infiltrate into gastrointestinal tissue, resulting in gastrointestinal dysfunction. Here, we report a case of pediatric eosinophilic gastroenteritis (EGE). A 7-year-old boy with multiple food allergies (cow milk, hen's egg, fish,shellfish, and chicken) was admitted to our hospital because of continuous abdominal pain and vomiting. His soy allergy had been diagnosed to have oral tolerance based on an oral food challenge at the age of 6 years. He was diagnosed with EGE based on biopsy findings showing eosinophilic infiltration ( 20 eosinophils per high-power field) into the gastrointestinal mucosa. A diet eliminating soy, wheat, beef, pork, rice, and sesame in addition to the food that had already been eliminated and oral corticosteroids improved his symptoms and peripheral eosinophilia. A relapse of both abdominal pain and peripheral eosinophilia after the reintroduction of soy or pork identified them as foods causative of EGE. This report highlights the utility of elimination diets in improving EGE symptoms and the subsequent reintroduction of offending foods in identifying causative foods. Furthermore,EGE onset should be considered when introducing potentially allergic food in the management of food allergy. J. Med. Invest. 66 : 201-204, February, 2019.

Eosinophilic gastrointestinal diseases (EGIDs) are divided into eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE), depending on the involved gastrointestinal tract, though both are considered to be chronic Th2-type allergic diseases caused by food or environmental allergens. In development of EoE, refluxed gastric acid may also have an important role. For diagnosis of EGIDs, the presence of symptoms possibly originating from the involved gastrointestinal tract and dense eosinophil infiltration are important factors. Imaging studies, including endoscopy and computed tomography, along with histopathological examinations of biopsy specimens are useful for diagnosis, whereas laboratory testing of blood, urine, and stool samples has limited value. Three useful options for treating EoE patients are acid inhibitors, swallowed topical corticosteroids, and an elimination diet, while systemic administration of glucocorticoids is the standard treatment of EGE, though information is limited. Since the prevalence of EGIDs is increasing in Western countries as well as Japan, development of effective treatments based on sufficient evidence is becoming an urgent need.