Eosinophilic Gastrointestinal Disorders Research Articles

S222 Patients With Eosinophilic Colitis Have Comparable Rates of Colorectal Cancer Compared to Patients With Ulcerative Colitis

Introduction: Eosinophilic colitis (EoC) is a rare entity characterized by the presence of high eosinophilic infiltrate into the colonic wall in symptomatic patients, in the absence of known other causes of colonic eosinophilia. Recently proposed guidelines suggest 100 eosinophils per high-power-field in the ascending colon, 85 in the descending, and 65 in the sigmoid colon as diagnostic thresholds. Whereas ulcerative colitis (UC), is known to be associated with an increased risk of colorectal cancer (CRC), little is known of the association between EoC and CRC. We aimed to compare EoC patients to UC patients to assess their odds of developing CRC. Methods: Using the multi-institutional, health research network database TriNetX (Cambridge, MA), de-identified, aggregated clinical data were obtained on patients with a diagnosis of either EoC or UC. Patients with other identifiable causes of eosinophilia were excluded from the EoC cohort, including inflammatory bowel disease, food allergies, helminth infections, and other eosinophilic gastrointestinal disorders. A 1:1 propensity score matching method was used to stratify EoC and UC patients. Matched variables were age at diagnosis, sex, race, obesity, tobacco abuse, alcohol abuse, and family history of digestive tract malignancy. Odds ratios(OR) and confidence intervals (CI) were calculated for development of CRC and subsequent colonoscopies for each cohort. Results: A total of 1,310 and 195,477 EoC and UC patients were identified, respectively (Table). The higher proportion of EoC patients were female compared to UC patients (65.4% vs 54.4%), and were African American (11.9% vs 9.2%). More EoC patients reported tobacco usage (4.6% vs 2.5%) and were obese (11.8% vs 7.0%) compared to UC patients. A 1:1 matching ratio stratified 1,310 patients into each cohort. After adjusting for the aforementioned covariates, EoC patients had an OR of 1.304 (95% CI 0.828-2.054, p-value 0.2503) of developing CRC compared to UC patients (Figure). EoC patients demonstrated an OR of 0.754 (95% CI 0.583-0.976, p-value 0.0313) of undergoing subsequent surveillance colonoscopies after initial diagnosis of disease compared to UC patients. Conclusion: Patients with a diagnosis of EoC have a similar risk of developing colorectal cancer compared to UC patients. Despite this, EoC patients are less likely to undergo subsequent surveillance colonoscopy compared to UC patients. Hopefully, our data can be used for future prospective studies investigating the natural course of EoC.Figure 1.: Forest plot showing odds ratios and confidence intervals of development of colorectal cancer (CRC) and subsequent surveillance colonoscopies in EoC patients compared to UC patients Table 1. - Baseline patient characteristics of EoC (eosinophilic colitis) and UC (ulcerative colitis) patients before and after 1:1 propensity score matching Baseline Patient Characteristics Before Matching p-value After Matching p-value EoC(n=1,310) UC(n=195,477) EoC(n=1,310) UC=n1,310) Age at Diagnosis 54 +/- 17.2 51 +/- 17.6 < 0.0001 54 +/- 17.2 54 +/- 17.4 0.9451 Sex Female 857(65.4%) 106,402(54.4%) < 0.0001 857(65.4%) 865(66.1%) 0.7419 Male 453(34.6%) 89,075(45.6%) < 0.0001 453(34.6%) 445(33.9%) 0.7418 Race African American 157(11.9%) 17,934(9.2%) 0.0005 157(11.9%) 134(10.2%) 0.1527 Asian 32(2.4%) 3,583(1.8%) 0.1014 32(2.4%) 39(2.9%) 0.3997 Caucasian 980(74.8%) 145,147(74.3%) 0.6468 980(74.8%) 1,007(76.9%) 0.2178 Other/Unknown 141(10.9%) 28,813(14.7%) < 0.0001 141(10.9%) 130(10.0%) 0.6152 Other Covariates Alcohol abuse 18(1.4%) 3,241(1.7%) < 0.0001 18(1.4%) 151(11.5%) 0.8078 Family history of GI cancer 38(2.9%) 4,033(2.1%) < 0.0001 38(2.9%) 49(3.7%) 0.2818 Obesity 155(11.8%) 13,688(7.0%) 0.4222 155(11.8%) 12(0.9%) 0.2706 Tobacco use 60(4.6%) 4,807(2.5%). 0.0338 60(4.6%) 31(2.4%) 0.3931

S3390 Celiac Disease and Systemic Eosinophilia: A Case Report

Introduction: Celiac disease is an immune mediated reaction to the gluten protein. this disease primarily affects the small intestine.it occurs in population with genetic predisposition, usually resolves with gluten free diet regimen. it was reported the association between eosinophilic gastrointestinal diseases and celiac disease but in the following case will discuss patient with significant peripheral eosinophilia and celiac disease without Eosinophilic gastrointestinal disorder. Case Description/Methods: 45 years old male, with history of hypertension, who presented with progressively worsening intermittent colicky lower abdominal pain for the past 2 months. Associated with recurrent episodes of nausea and vomiting, and non-bloody watery diarrhea.Patient Labs were significant for Hemoglobin 12 gm/dL, WBC’s 26,000 with 62% Eosinophils (16,500 /uL), Platelet of 332 Thou/uL. Peripheral blood smear was negative for parasites, stool was negative for parasites or bacterial infection. Patient went upper GI endoscopy that showed grade A reflux esophagitis, congestive gastropathy, Duodenitis, and non-bleeding gastric ulcer, Biopsies were obtained during the EGD. Pathology showed Duodenal mucosa with mild villous atrophy and focal increased intraepithelial lymphocytes suggestive of celiac disease,chronic gastritis, esophageal biopsy was negative for increased eosinophils. Patient was started on gluten free diet that was resulted in gradual resolution of his symptoms and also normal eosinophilic count after 1 month. (Figure) Discussion: Patient with celiac disease can present with typical gastrointestinal symptoms such as diarrhea, weight loss, bloating, abdominal pain, and also non-gastrointestinal abnormalities such as abnormal liver function test, iron deficiency anemia, and it may be asymptomatic. In this case patient presented with typical symptoms but was associated with significant peripheral eosinophilia, without evidence eosinophilic gastrointestinal disorder.Figure 1.: EGD showing stomach and duodenum.

S2264 A Case of Progressive Untreated Eosinophilic Gastrointestinal Disorder Complicated by Eosinophilic Myocarditis

Introduction: Eosinophilic gastrointestinal diseases (EGID) are immune-mediated conditions characterized by GI dysfunction and histological evidence of eosinophilic infiltration. While usually confined to the GI tract, severe inflammation can involve multiple organ systems, typically under the umbrella term of hypereosinophilic syndrome (HES). Patients can present with cardiac involvement such as eosinophilic myocarditis which results in an uncommon, but potentially lethal complication. We present a case of a patient with prior history of eosinophilic esophagitis (EoE) subsequently presenting with diffuse EGID complicated by eosinophilic myocarditis. Case Description/Methods: A 63-year-old female with a history of EoE and breast cancer post mastectomy presented with acute epigastric and chest pain. The patient had biopsy-proven EoE which was managed with PPI in the past. On physical examination, she had diffuse abdominal tenderness. Labs were remarkable for peripheral eosinophilia peaking at 57%. Initial high sensitivity troponin I was 300 ng/L without EKG changes, and ultimately peaked at 7821 ng/L. CT of the abdomen and pelvis showed thickening of the stomach, duodenum, and jejunum. Left heart catheterization revealed LAD disease without obstructive disease. EGD demonstrated severe inflammation, erythema, and eosinophilic infiltration in the gastric body, antrum, and throughout the duodenum. High dose steroids were initiated with subsequent improvement in symptoms, serum troponin, and complete resolution of peripheral eosinophilia. Patient followed up as an outpatient, where cardiac MRI confirmed eosinophilic myocarditis, and she was started on Mepolizumab for maintenance therapy and prevention of relapse. Discussion: EGID are increasingly prevalent disorders that can result in significant morbidity and mortality without prompt diagnosis. This patient had a history of EoE and developed diffuse GI involvement and subsequent eosinophilic myocarditis. Her presentation as atypical chest pain suggestive of NSTEMI resulted in delay of initiation of steroids until after heart catheterization. Our case suggests that without glucocorticoid suppression, eosinophilia can cause widespread tissue infiltration and damage. The majority of these patients have chronic disease that require long term maintenance therapy. Mepolizumab has been demonstrated to be an effective agent for hypereosinophilic disorders. When managing EGID, it is pertinent to recognize early involvement of systemic eosinophilic infiltration.Figure 1.: EGD.

Utility of Diagnostic Colonoscopy in Pediatric Intestinal Disease.

Background: The roles and methods of diagnostic colonoscopy in pediatric patients were previously demonstrated. With advances in medical equipment and the increasing need for pediatric endoscopic diagnosis, we compared recent results with those previously reported. Methods: A retrospective analysis was conducted on pediatric patients aged ≤15 years, comparing those who underwent their first diagnostic colonoscopy between 1 January 2007 and 28 February 2015 with those who did so between 1 March 2015 and 28 February 2022 at Kurume University Hospital. Results: A total of 274 patients were included, including 110 in the previous study and 164 in the present study. The main indications were hematochezia in the previous study (63/110, 57.3%) and abdominal pain in the present study (64/164, 39.0%). Ulcerative colitis (74/274, 27.0%) was the most common diagnosis in both studies. The major difference from the previous study was an increase in the number of Crohn’s disease and eosinophilic gastrointestinal disorder cases. Bowel preparation with magnesium citrate was significantly increased across all ages in the present study (142/164, 86.6%). Midazolam + pentazocine was used for sedation in most cases (137/164, 83.5%). An ultrathin upper endoscope was mainly used in patients aged ≤6 years, while ultrathin colonoscopes were applied in patients aged 7–12 years. Conclusion: In the present study, appropriate changes were found in the roles and methods of diagnostic colonoscopy in pediatric patients compared to the previous study. The increasing trend of patients presenting with inflammatory bowel disease and eosinophilic gastrointestinal disorder worldwide indicates the importance of colonoscopy in infants and children.

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

RationaleEosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals.MethodsWe queried the U.S. Immunodeficiency Network (USIDNET) for patient records including the terms eosinophilic esophagitis, gastritis, enteritis, or colitis. We analyzed 74 patient records from the database, including diagnoses, demographics, infectious history, laboratory findings, genetic studies, therapeutic interventions, and clinical outcomes.ResultsWe examined 74 patient records. A total of 61 patients had isolated EoE, and 13 had distal gastrointestinal involvement consistent with EGID. The most common IEI were common variable immunodeficiency (43.2%), some form of combined immunodeficiency (21.6%), chronic granulomatous disease (8.1%), hyper-IgE syndrome (6.8%), and autoimmune lymphoproliferative syndrome (6.8%). The median age at presentation with IEI was 0.5 years (IQR 1.725, max 39 years) and 56.76% were male. Approximately 20% of the patients in the cohort received a hematopoietic stem cell transplantation for treatment of IEI, but the timing of the HSCT in relationship to the EGID diagnosis was unknown.ConclusionsHere, we report EGID in a diverse cohort of IEI patients, suggesting that both non-EoE EGID and EoE can be seen as comorbid conditions with a variety of IEI. Our data suggests that EGID may be more common in patients with IEI than would be expected based on estimates of EGID in the general population.

Eosinophilic gastrointestinal disorders in childhood

Eosinophilic gastrointestinal disorders are a group of chronic inflammatory conditions characterised by the presence of eosinophilic infiltrates in the gastrointestinal wall. These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Their incidence is increasing, with eosinophilic esophagitis known to be the most common form. The etiopathogenesis of eosinophilic gastrointestinal disorders is not fully understood, and most likely associated with an abnormal immune response to food and/or inhalant allergen. They are often accompanied by allergies. Clinical symptoms, especially in the youngest children, are non-specific and depend on the gastrointestinal segment involved. These are most often feeding difficulties and regurgitation in infants, and heartburn, chest pain, dysphagia and food bite impaction in adolescents and adults. Except for eosinophilic esophagitis, there are no uniform diagnostic or therapeutic guidelines for eosinophilic gastrointestinal disorders. Diagnosis is challenging and it is based on the coexistence of clinical, endoscopic and histopathological symptoms and the exclusion of secondary causes of gastrointestinal eosinophilic infiltration. Treatment involves the use of proton pump inhibitors, an elimination diet, or glucocorticoid therapy. Endoscopic or surgical treatment may be necessary in some cases. Clinical remission does not correlate with histopathological remission, therefore monitoring of therapeutic effects requires multiple endoscopies with histopathological assessment of specimens. The aim of this paper was to present the current data on the incidence, diagnosis and treatment of eosinophilic gastrointestinal diseases in children.

A rare case of eosinophilic gastrointestinal disorders with short bowel syndrome after strangulated bowel obstruction

BackgroundShort bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction.Case presentationA 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence.ConclusionThe risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination.

Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis.

The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase β2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.

Mortality and cancer in eosinophilic gastrointestinal disorders distal to the esophagus: nationwide cohort study 1990–2017

BackgroundEosinophilic 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.MethodsNationwide, 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.ResultsIn 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.ConclusionsThis 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.

Ruxolitinib Treatment in an Adolescent With Chronic Graft-Versus-Host Disease Mimicking Eosinophilic Gastrointestinal Disorders: A Case Report

Eosinophilic gastrointestinal disorders (EGIDs) are well-documented entities in pediatric solid organ transplantation. However, the diseases are rare after bone marrow transplantation (BMT). We present an adolescent male with hemoglobin E-β-thalassemia who underwent BMT and developed chronic graft-versus-host disease (GVHD) mimicking EGIDs. Initially, the patient presented with a presumed diagnosis of eosinophilic gastroenteritis (subserosal type) and received corticosteroids for 12 weeks. Six months after corticosteroids cessation, he again developed abdominal pain, treated with corticosteroids, azathioprine, and a six-food elimination diet. Still, he later had similar symptoms with persistent hypereosinophilia. The patient was subsequently diagnosed with chronic GVHD after excluding various potential causes. Ruxolitinib also led to significant clinical improvement and the disappearance of eosinophilia. The differential diagnosis of chronic GVHD should be a concern in BMT recipients with persistent gastrointestinal symptoms and eosinophilia. Ruxolitinib may be a treatment option in children with a steroid-refractory disease.

Eosinophilic Disorders of the Gastrointestinal Tract and Associated Abdominal Viscera: Imaging Findings and Diagnosis.

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.

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders.

The incidence and prevalence of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC) are increasing ( 1 ). These conditions will inevitably become more widely recognized and better understood. There is currently no Food and Drug Administration (FDA)-approved treatment for EoE, but there are standard-of-care treatments that are well established and widely used. In contrast, there is a paucity of data regarding standard-of-care treatment for non-EoE eosinophilic gastrointestinal disorders (EGID). We identified 3 patients that all achieved clinical and histopathologic remission on dupilumab, a monoclonal antibody that blocks the downstream signaling of interleukin (IL)-4 and IL-13. These patients had extra-esophageal forms of EGID with two patients failing to achieve remission on standard-of-care therapies and one patient experiencing significant side effects on swallowed budesonide therapy. The reduction in mucosal eosinophilia in several GI tract segments in these 3 patients highlights a new potential clinical indication for dupilumab in the treatment of pediatric EGID patients.

Eosinophilic gastrointestinal disorders presenting with multiple gastric and colonic ulcerative lesions: a case report

Eosinophilic gastrointestinal disorders are rare inflammatory conditions marked by eosinophilic infiltration of the gastrointestinal tract. Endoscopic manifestations vary from patient to patient. However, ulcerative lesion is a rare occurence. A 57-year-old patient presented with chronic diarrhea and significant peripheral blood eosinophilia. During endoscopy, multiple ulcers were discovered throughout the stomach, duodenum, and colon. Biopsies showed excess tissue eosinophilia suggestive of eosinophilic gastroenteritis and colitis. The patient responded dramatically with corticosteroid. However, he developed steroid dependency necessitating the use of azathioprine. In conclusion, a rare case of eosinophilic gastroenteritis and colitis presented with multiple ulcerative lesions was described. Physicians should be aware that eosinophilic gastroenteritis and colitis may be a cause of chronic diarrhea, particularly, in patients presented with peripheral blood eosinophilia. Corticosteroid is the mainstay of treatment. In steroid dependency case, azathioprine may be an option.

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+ eosinophils unique to the small intestine

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.

Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Primary eosinophilic gastrointestinal disorders (EGID) are increasingly prevalent, immune‐mediated, chronic conditions which primarily affect pediatric and young adult patients, leading to substantial disease burden, and poor quality of life. EGID may either involve single portions of the gastrointestinal tract (i.e., esophagus, stomach, small bowel, and colon) or a combination. Their strong association with allergic disorders has been recently recognized, and although their shared pathophysiological basis remains partly elusive, this feature greatly impacts the diagnostic and treatment work‐up. We herein critically discuss the current knowledge on the association of EGID and allergic disorders, including atopic dermatitis, allergic rhinitis, allergic asthma, and food or drug allergy. In particular, we reviewed the literature focusing on their epidemiology, pathophysiological basis and mechanisms, and diagnostic strategies. Finally, we discuss the currently ongoing clinical trials targeting EGID and allergic diseases, including, among others the monoclonal antibodies dupilumab, mepolizumab, benralizumab, and lirentelimab.

Improving Care in Eosinophil-Associated Diseases: A Charter.

Eosinophil-associated diseases (EADs) are a range of heterogeneous conditions in which eosinophils are believed to play a critical pathological role. EADs include common illnesses such as eosinophilic asthma and chronic rhinosinusitis and rare conditions such as hypereosinophilic syndromes (HES) and eosinophilic gastrointestinal disorders (EGIDs). EADs are associated with substantial burdens for the patient, including chronic, debilitating symptoms, increased financial burden, decreased health-related quality of life, and the need for repeated visits to multiple different healthcare professionals (HCPs), emergency departments, and/or hospitals. Poor EAD recognition by HCPs often contributes to delayed diagnoses, which further delays patient access to appropriate care and effective treatments, contributing to poor health outcomes. The objective of this charter is to outline key patient rights and expectations with respect to the management of their condition(s) and to set forth an ambitious action plan to improve health outcomes for patients with EADs: (1) people with EADs, their caretakers, HCPs, and the public must have greater awareness and education about EADs; (2) people with EADs must receive a timely, accurate diagnosis; (3) all people with EADs must have access to an appropriate multidisciplinary team, when necessary; and (4) people with EADs must have access to safe and effective treatment options without unnecessary regulatory delays. The principles described in this charter demonstrate the core elements of quality care that people with EADs must receive, and they represent clear steps by which to reduce patient and caregiver burden and improve patient outcomes. We urge HCPs, healthcare systems, and policymakers worldwide to swiftly adopt these principles to ensure patients with EADs have an accurate diagnosis in a timely manner and access to high-level care and treatment in an appropriate setting.Graphic abstract

Transition of care of patients with eosinophilic gastrointestinal diseases: Challenges and opportunities.

Eosinophilic gastrointestinal disorders (EGID) are a group of allergen-mediated conditions which are characterized by eosinophilic inflammation affecting one or more parts of the gastrointestinal tract. A disproportionately higher number of EGID patients are diagnosed in the pediatric age group. Given the chronic course of EGIDs and lack of curative therapies at this time, majority of the pediatric EGID patients may require continued care well into their adulthood. However, to date, scant data are available regarding the health care transition (HCT), the transition of care (TC), and the effectiveness of transfer of care EGID patients from pediatric-oriented to adult-oriented providers. Herein, we review the lessons learnt from transfer of care of children with other chronic gastrointestinal and allergic conditions, analyze the current knowledge, potential barriers, the role of various stakeholders in successful transfer of care of EGID patients, propose a conceptual framework for HCT and TC of EGID patients, and identify outcome measures to ensure the quality of progression of care.

Dupilumab: A Review of Present Indications and Off-Label Uses.

Recent advances in our understanding of T2 inflammation have revealed more diseases in which T2 inflammation is involved. Dupilumab is a recently developed monoclonal antibody that blocks signaling of IL-4 and IL-13, both of which are crucial cytokines in the T2 response. New possible indications are increasingly explored and include skin diseases, such as prurigo nodularis, nummular eczema, allergic contact dermatitis, chronic hand eczema, spontaneous chronic urticaria, bullous pemphigoid, alopecia areata, and Netherton syndrome, as well as respiratory diseases, such as allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and allergic rhinitis. In addition, eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, and food allergy, are also research fields of interest. Here, we review published data and clinical trials examining the use of dupilumab in these disorders.

Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease

Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology. To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders. Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n= 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882). Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05). Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis

COVID-19 infection in hypereosinophilic syndrome: A survey-based analysis