Eosinophilic Gastrointestinal Diseases Research Articles

Mast Cell Numbers in Primary Eosinophilic Colitis are Significantly Higher than in Secondary Tissue Eosinophilia and Normal Control: a Possible Link to Pathogenesis.

Primary Eosinophilic Colitis (PEC) is one of the rare eosinophilic gastrointestinal diseases with a poorly understood pathogenesis. Eosinophilic esophagitis (EE) is the most common and best-understood disease in this category. Activated mast cells (MCs) have a role to play in the tissue damage in EE. It is not known if PEC shares this mechanism. This cross-sectional study aimed to investigate the number of MCs in PEC and to compare them with cases of secondary colonic tissue eosinophilia (TE) and normal colon. The study included 19 PEC cases, 47 cases of secondary tissue eosinophilia and 50 normal colon tissues. Histopathological slides of all cases were reviewed to confirm the diagnosis and count the number of eosinophils. Glass slides for all cases were stained for C-kit (CD117) to highlight and count the MCs. The mean number of the MCs in normal controls was 9.7 MCs per HPF (SD= 4.6). The mean number of MCs in the PEC cases was 26.5 (SD=7.1) which was significantly higher than the normal counts (p-value <0.000). The mean number of MCs in the secondary TE group was 18.0 (SD=7.1), which was significantly higher than normal controls; p-value <0.000. Comparing MC counts in PEC and secondary TE also revealed a significant difference with a p-value of < 0.000. MCs in PEC are significantly higher than those in secondary TE and normal controls. This suggests the role of the MCs in the pathogenesis of Primary Eosinophilic Colitis.

Emerging Therapies for Eosinophilic Gastrointestinal Diseases

Besides eosinophilic esophagitis, other eosinophilic gastrointestinal diseases (EGIDs), such as eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis, are increasingly diagnosed over the last decade. Whereas diagnosis and therapy of eosinophilic esophagitis have been standardized, the diagnosis and therapy of other EGIDs are areas of active research. Motivated by the increasing prevalence of these conditions, concerted efforts of different stakeholders have led to the evaluation of targeted biologic therapies for EGID management over the last couple of years, and several promising molecules are currently in the pipeline. This review article provides an overview of targeted biologic therapies for use in EGIDs.

From the Pages of AllergyWatch: October 2021

For this issue of From the Pages of AllergyWatch, I have chosen 3 recent reviews of interest. The first, reviewed by Dr Lee, reports on the relationship of tryptase genotyping on patients with systemic mastocytosis. The next, reviewed by Dr Hernandez-Trujillo, presents data on the increased sleep problems in urban children with asthma and atopic dermatitis. The final review, from Dr Chipps, reports on a novel anti–Siglec-8 antibody reducing gastrointestinal eosinophilia in patients with eosinophilic gastrointestinal disease.

Clinical Characteristics and Outcomes of Eosinophilic Colitis in Patients With Cancer.

Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria of colonic mucosa. The pathophysiology is unclear, but EoC has been associated with multiple known risk factors. The aim of this study was to characterize the clinical characteristics and disease course of patients with EoC at a major cancer center. We retrospectively reviewed colonic samples obtained between January 2000 and December 2018 from our institutional database and included cases with significant colonic eosinophilia. Baseline clinical data and EoC-related clinical course and outcomes were documented. Forty-one patients were included. One fourth had coexisting autoimmune conditions. Seventy-eight percent had a cancer diagnosis. Half the patients received chemotherapy, with a median duration of 180 days between chemotherapy and EoC onset. Symptoms were present in 76% of patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs. 42%). Median duration of EoC symptoms was 30 days in patients with cancer and 240 days in those without cancer (P=0.03). Most patients (88%) had normal colonoscopy findings. Fifteen percent of patients required hospitalization. All-cause mortality was 37%, mostly related to underlying malignancy and organ failure. EoC in cancer patients appears to have more diarrhea-predominant symptoms, particularly in patients receiving chemotherapy, but a shorter disease duration compared with patients without cancer. Hospitalization can be required for serious cases. Treatment may be reserved for patients requiring symptom management, as most patients with EoC have good clinical outcomes regardless of treatment.

The use of biologics in food allergy.

Food allergy continues to pose problems due to its increased frequency and its increasingly high severity. In this context, alongside the traditional avoidance strategies of allergenic foods and desensitization through the cautious progression of exposure to foods in the context of oral immunotherapy (OIT), alternative strategies have made their way in the last decades. We review the possibilities of intervention in food allergy with the use of biological drugs capable of interfering with the synthesis of IgE, with their mechanisms of action, or with complex biological mechanisms that lead to the establishment of a food allergy. Repeated Entrez PubMed searches using the template algorithm "Food allergy" and "biologics" or "Omalizumab" or "Dupilumab" or "milk desensitization" or "oral tolerance induction" or "oral immunotherapy" or "Etokimab" or "Tezepelumab" or "Quilizumab" or "Ligelizumab" or "Tralokinumab" or "Nemolizumab" or "Mepolizumab" or "Reslizumab" or "Benralizumab". The authors' clinical experience in paediatric allergy units of University hospitals was also drawn upon. The landscape in this context has changed dramatically over the past 10years. We have acquired knowledge mainly on the effect of different types of anti-IgE treatments in poliallergic patients with food allergy, and in patients treated with OIT. However, other mediators are being targeted by specific biologic treatments. Among them, the alarmins Il-33 and TSLP, IL-4 and IL-13, eosinophil-related molecules as IL-6, IL-8, IL-10, IL-12, and mostly IL-5, and integrins involved in the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), as SIGLEC-8. The ever-better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis

Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf). Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. Among 100 patients (n= 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ= 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P= .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ= -0.38; P= .157 for ≤1 y and ρ= 0.02; P= .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P= .183) and 0.78 (P= .494), respectively. Dilation modified the association between symptoms and eos/hpf (P= .005 and P= .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively). In nondilated EoE adults, eos/hpf correlate modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.

Psychiatric Comorbidities Are Highly Prevalent in Nonesophageal Eosinophilic Gastrointestinal Diseases

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.

A Summary of the Meetings of the Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) International Multidisciplinary Consensus

A Summary of the Meetings of the Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) International Multidisciplinary Consensus

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): An International Multidisciplinary Consensus

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS): An International Multidisciplinary Consensus

Pathogenic effector TH2 cells discriminate between allergic and eosinophilic inflammation in food allergy and eosinophilic gastrointestinal disease

Abstract IgE-mediated food allergies (FA) and delayed food-triggered (FT) gastrointestinal tissue eosinophilia (EGID) have distinct clinical manifestations and are treated differently. Pathogenic effector TH2 (peTH2) cells are implicated in inappropriate TH2 responses in both of these diseases. Furthermore, EGID patients can have concomitant FA, and some EGID patients do not report any food triggers. To better understand the role of peTH2 cells in the context of FA and EGID and the overlap between these two conditions, peTH2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) from purified peripheral blood mononuclear cells (PBMC) were profiled by intracellular cytokine flow cytometry in these deeply-characterized patient cohorts: patients with FA alone (FA, n=5), EGID with FA and FT (EGID+FA+FT, n=7), EGID with FT (EGID+FT, n=7) and EGID without FA or FT (EGID, n=9). Patients with any food allergy or food trigger (FA, EGID+FA+FT, and EGID+FT) have increased peTH2 cells compared to healthy volunteers (HV). Interestingly, a greater percentage of peTH2 cells in patients with food triggers (EGID+FA+FT, EGID+FT) exhibit a trend toward IL5+IL13+ double positivity (P = 0.0556) than those from patients without food triggers (FA, EGID). In contrast, peTH2 cells from patients with FA had a greater percentage that were IL17A+ (P=0.009) or IFNγ+ (P=0.0444) than patients with eosinophilic disease (EGID+FA+FT, EGID+FT, EGID). Our studies indicate that while elevated levels of peTH2 cells are indicative of allergic inflammation of both immediate hypersensitivity and eosinophilic disease, the cytokine profile of each disorder may be distinct, where IL17A+ and IFNγ+ predominate in those without eosinophilic disease.

Primary Eosinophilic Gastrointestinal Diseases Beyond Eosinophilic Esophagitis in Children.

There are many unknowns about primary eosinophilic gastrointestinal disease (EGID) in childhood. The aim of this study is to provide data about the frequency, management, control level, and prognosis of well documented primary EGID in childhood. This study was conducted in children who underwent endoscopy and/or colonoscopy at a single center over 10-year period up to August 2018. Primary EGID was diagnosed after exclusion of secondary EGID and classified as eosinophilic gastritis (EG), eosinophilic enteritis (EE), eosinophilic gastroenteritis (EGE: eosinophilic gastritis with eosinophilic enteritis) and eosinophilic colitis (EC) according to histopathological evaluation. The pathological number of eosinophil counts were accepted as >30 hpf for gastric mucosa in 5 hpf area, ≥20/hpf for duodenal, jejunal, and ileal mucosa, >50/hpf for right colonic mucosa, >35/hpf for transverse colonic mucosa, and >25/hpf for left colonic mucosa. Presenting symptoms, signs, management, follow-up, disease control level, and remission were analyzed. Remission is defined if the patient is controlled with all clinical, endoscopic/colonoscopic, and histopathologic parameters without any treatments or diet for at least a year. During the study period, 7457 biopsies were taken in 8262 endoscopy and/or colonoscopy procedures. Primary and secondary EGID frequencies were found 0.23% (n = 17 patients) and 0.1% (n =8 patients) per procedure with biopsy in children, respectively. Endoscopy/colonoscopy procedures were not able to performed in 9 patients because of short follow-up period (n = 6) or patients leaving follow-up (n = 3). Nine of the primary EGID patients had esophageal eosinophilia (EsE) at the time of diagnosis, 5 of them were previously managed as EoE. The median follow-up period of primary EGID patients excluding the ones without a control endoscopy/colonoscopy procedure was 3.35 years (min-max: 1.1-9.0 years). Proton pump inhibitors (PPI) were the most frequently used treatment alone or in combination with diet, systemic and/or topical corticosteroids. Disease control was evaluated in 8 of 17 patients and it was uncontrolled in 4, partially controlled in 1, and controlled in 3 patients. Remission was achieved in 2 patients. The frequency of primary EGID beyond eosinophilic esophagitis (EoE) in children is low. It may be difficult to achieve control in children with primary EGID in the long-term follow-up.

Eosinophilic esophagitis. What diet? How to treat it? The point of view of a gastroenterologist working in a department of allergology

Eosinophilic esophagitis (EoE) belongs to a broad group of allergic gastrointestinal diseases. More narrowly, it is classified as an eosinophilic gastrointestinal disease and is its most common representative. Until recently, this disease was extremely rare, but the last 3 decades have seen a rapid increase in its prevalence to such an extent that in some recent studies it has been named the most common esophageal disease after reflux disease. EoE is an interdisciplinary disorder on the borderline between gastrointestinal and allergologic diseases, requiring cooperation of these two branches of medicine in diagnostics and treatment. Despite the development of medical science it remains a poorly known disease, difficult to diagnose and even more difficult to treat. Recent years have seen the emergence of new studies and guidelines, both American and European, that have radically changed our approach to the diagnosis and treatment of EoE.

Esophageal Fibrosis in Eosinophilic Gastrointestinal Diseases.

Eosinophilic esophagitis (EoE), the most common eosinophilic gastrointestinal disease (EGID), is associated with lamina propria (LP) fibrosis. The relationship of EoE to other EGIDs is still unclear. We frequently observe cases of concurrent esophageal eosinophilia and extra-esophageal mucosal eosinophilia. The purpose of this study was to compare clinical, endoscopic, and histologic features, as well as the prevalence of esophageal LP fibrosis in children with EGID and concurrent esophageal eosinophilia to children with EoE. We also examine the current practices of pathologists in evaluating fibrosis. We reviewed esophageal biopsies from index cases of EoE (N = 38), EGID with significant esophageal eosinophilia (≥15 eos/hpf) (EGID-SEE, N = 38), EGID with mild esophageal eosinophilia (1-14 eos/hpf) (EGID-MEE, N = 12), and EGID with no esophageal eosinophilia (EGID-NEE, N = 12) for LP presence, adequacy, and fibrosis. EoE and EGID-SEE cases share similar demographics, esophageal endoscopic features, and symptoms. A majority of EGID-SEE cases (71%) had adequate LP for the evaluation of fibrosis, similar to EoE cases (87%). The prevalence of esophageal fibrosis in EoE (79%) and EGID-SEE (55%) cases were similar, whereas no fibrosis was detected in the EGID-MEE and EGID-NEE cases. The fibrosis was patchy and often detected in the distal esophagus. Fourteen cases were reclassified from their original clinical diagnosis as having fibrosis by the study pathologists. Cases of EGID-SEE have overlapping features with EoE, suggesting that all EGIDs are part of a disease continuum. A consensus for the evaluation of LP fibrosis is needed.

M264 AN UNUSUAL CASE OF EOSINOPHILIC GASTROINTESTINAL DISEASE INVOLVING THE LIVER

Eosinophilic gastrointestinal disease (EGID) is a collection of rare infiltrative diseases in which eosinophils invade the digestive tract and can manifest common symptoms.

Upper Gastrointestinal Bleeding as the First Presentation of Eosinophilic Gastrointestinal Disease.

Gastrointestinal bleeding is a rare but potentially life-threatening manifestation of eosinophilic gastrointestinal disorders (EGIDs). Here, we describe a case series comprising 5 pediatric patients between 7 and 12 years of age, who presented to the emergency department with hematemesis and were subsequently diagnosed with EGID. Accompanying allergic history, peripheral eosinophilia, and total IgE elevation were common. Despite a more severe presentation, response to medical and dietary therapy was favorable. A comprehensive review of the literature revealed 26 other cases with similar findings that reinforced the importance of prompt recognition and early dietary and immunomodulating therapy in the control of this disease.

Disease Course and Treatment Response of Eosinophilic Gastrointestinal Diseases in Children With Liver Transplantation: Long-Term Follow-Up.

To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. Of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P ≤ 0.0001), transplanted more frequently due to biliary atresia (P ≤ 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P ≤ 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.

S1330 High Discovery Rate of Previously Undiagnosed Patients With Eosinophilic Gastritis and Duodenitis Using a Systematic Endoscopic Biopsy Protocol: Screening Data Analysis From ENIGMA, a Randomized Controlled Trial

INTRODUCTION: Eosinophilic gastrointestinal (GI) disorders (EGIDs) such as eosinophilic gastritis (EG) and duodenitis (EoD) are chronic inflammatory conditions characterized by aberrant accumulation and activation of localized tissue eosinophils and mast cells. Patients (pts) with EG/EoD present with non-specific, often debilitating GI symptoms including abdominal pain and cramping, early satiety, nausea and diarrhea. Non-specific symptoms, the absence of consensus diagnostic histopathologic guidelines, and the perception of rarity contribute to a delay in diagnosis of pts with EG/EoD. While the prevalence of EG/EoD is currently estimated to be ∼50,000 in the US, this may be an underestimate. We aimed to evaluate the prevalence of EG/EoD among symptomatic patients not previously diagnosed. METHODS: We reviewed screening data from ENIGMA, a multi-center, randomized, double-blind, placebo-controlled phase 2 trial assessing the safety and efficacy of AK002, an anti-Siglec-8 monoclonal antibody, in pts with EG/EoD. Adult pts were screened with a validated, daily 8-symptom EG/EoD questionnaire to capture moderate-severely symptomatic pts. Those who met symptom inclusion criteria underwent upper endoscopy (EGD) with gastric and duodenal biopsies as per protocol (12 total: 4 biopsies each from the gastric antrum, gastric corpus, and duodenum). Symptomatic pts meeting histologic definition of EG (≥30 eos/hpf in ≥5 hpfs) and/or EoD (≥30 eos/hpf in ≥3hpfs) were eligible for randomization. RESULTS: 113 pts entered screening for ENIGMA. 51 had no prior history of EG/EoD, 26 (51%) of whom met symptom criteria and underwent screening endoscopy. Of these 26 symptomatic pts, 15 (58%) met histologic criteria for EG/EoD, 13 of whom were randomized in the study. These 13 pts, previously given functional GI diagnoses, were clinically similar in constellation and magnitude of symptoms compared to the 52 randomized pts with previously established EG/EoD. CONCLUSION: There is growing evidence that EG/EoD is underdiagnosed, and that the true US prevalence may be higher than 50,000. Among moderate-severely symptomatic pts without known history of EG/EoD who entered screening for ENIGMA, 58% met histologic criteria for EG/EoD. EGD with multiple systematic gastric and duodenal biopsies of pts with chronic non-specific GI symptoms, including those with functional GI conditions, may demonstrate a higher prevalence of EG/EoD than is currently estimated.Figure 1.: Discovery Rate of Newly Diagnosed EG/EoD Patients in ENIGMA Screening 1) Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) sites; n = 62 entered screening 2) Primarily general gastrointestinal practices and professional GI research centers; n = 51 entered screening.Figure 2.: Similar Symptom Burden in Established and Newly Diagnosed EG/EoD Patients.Table 1.: Characteristics of Established and Newly Diagnosed EG/EoD Patients

Food allergy and eosinophilic gastrointestinal disorders.

Eosinophilic esophagitis (EoE) is a non-immunoglobulin E mediated disorder that has been seen with increasing frequency over the past 25 years. Although the presentation varies per age group from vomiting and refusal to eat in infants and toddlers to abdominal pain and dysphagia in school-aged children, and food impaction and indigestion in adolescents and adults. Treatment options include proton-pump inhibitors, dietary avoidance, swallowed steroids, or a combination of these. Newer therapies with biologics show promise in early studies. Cow's milk is the most common food trigger of EoE across all age groups, followed by wheat and eggs. Different dietary avoidance strategies have been used, and help from a knowledgeable nutritionist is often key to success. Patients with EoE commonly have other baseline atopic disease. Clinicians who take care of patients who are atopic, therefore, should have a higher index of suspicion for EoE in patients with dysphagia. The goals of treatment are both a decrease in symptoms and normalization of esophageal histology. Eosinophilic gastrointestinal diseases are less common and less likely to respond to dietary therapies and/or avoidance. Pathogenesis seems to be different and may be more autoimmune mediated. Trialing dietary restrictions is certainly an option in this cohort of patients. For persistent symptoms and abnormalities, systemic medications have been used, although biologics may be used in the future. Additional studies are needed to determine which patients will respond to which therapies.

Serum Interleukin-17 Evaluation in Patients With Eosinophilic Gastrointestinal Disease

Background: Eosinophilic gastrointestinal disorders or diseases (EGIDs) may result from an abnormal immune-mediated response to food antigens. Activated eosinophils release various mediators with inflammatory properties which may result in tissue and subsequently organ damage. The cytokine milieu of these patients has revealed increased levels of pro-inflammatory cytokines, including interleukin (IL)-17. This study aims to evaluate the potential role of this cytokine in the pathogenesis of EGID.Materials and Methods: This prospective study was conducted at the Allergy Outpatient Clinic, Mofid Children Hospital, Tehran, Iran from January 2016 to January 2017. In this study, Serum IL-17 was determined in all the patients referred to the Allergy Clinic with a pathologic diagnosis of EGID. Results: The median (minimum and maximum) serum IL-17 level in patients with EGID, gastroesophageal reflux disorder (GERD), and healthy controls were 4.32 (0.00-6.383), 2.82 (0.00-3.231), and 3.6 (0.00-7.165) pg/mL, respectively. The results of the non-parametric analysis revealed no significant difference between the three groups regarding IL-17 (P=0.16). However, by classifying EGID in two separate groups with the involvement of upper (eosinophilic esophagitis and eosinophilic gastritis) and lower (eosinophilic enteritis, eosinophilic colitis) gastrointestinal (GI) tracts, a significant difference in serum IL-17 level became evident (P=0.004). Conclusion: We found a significant relationship between IL-17 and upper GI involvement in EGID.

Eosinophilic Gastrointestinal Diseases in Children: A Practical Review.

Primary eosinophilic gastrointestinal diseases (EGIDs) represent a heterogeneous group of disorders characterized by eosinophilic inflammation in the absence of known causes for eosinophilia, selectively affecting different segments of the gastrointestinal tract. While pediatric eosinophilic esophagitis (EoE) is a well-defined disease with established guidelines, Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC) remain a clinical enigma with evidence based on limited anecdotal case reports. Large cross-sectional studies in the US defined a prevalence of EoG and EoGE ranging from 1,5 to 6,4/100.000 and from 2,7 to 8,3/100.000 subjects respectively, while the prevalence of EoC ranges from 1,7 to 3,5/100.000 subjects. Regarding the pathogenesis, it is hypothesized that EGIDs result from the interplay between genetic predisposition, intestinal dysbiosis and environmental triggers. Clinically, EGIDs might present with different and nonspecific gastrointestinal symptoms depending on the involved intestinal tract and the extension of eosinophilic inflammatory infiltrate. The diagnosis of EGIDs requires: 1. recurrent gastrointestinal symptoms, 2. increased eosinophils for high power field in biopsy specimens, 3. absence of secondary causes of gastrointestinal eosinophilia. No validated guidelines are available on the clinical management of patients with EGIDs. Evidence from case reports and small uncontrolled case series suggests the use of dietary and corticosteroids as the first-line treatments. Considering the clinical follow-up of EGIDs, three different patterns of disease course are identified: single flare, recurring course-disease and chronic course-disease. This review will focus on pediatric EGIDs distal to esophagus, including Eosinophilic Gastritis (EoG), Eosinophilic Gastroenteritis (EoGE) and Eosinophilic Colitis (EoC).