Eosinophilic Gastrointestinal Diseases Research Articles

Lobular panniculitis of the lower legs in a patient with eosinophilic gastrointestinal disease: A case report of scurvy.

Eosinophilic gastrointestinal disease (EGID) is a chronic condition that is commonly treated with restrictive food elimination diets, and may be complicated by food aversion. Here, we present a patient with recalcitrant EGID with lobular panniculitis of the lower legs secondary to scurvy. Cutaneous eruptions are the first manifestations of scurvy, and thus a high suspicion for panniculitis in the context of food restriction is critical to prevent further complications and mortality.

S667 Family History of Eosinophilic Esophagitis or Other Eosinophilic Gastrointestinal Disease Is Not Associated With Non-Response to Topical Steroid Treatment in Eosinophilic Esophagitis

S667 Family History of Eosinophilic Esophagitis or Other Eosinophilic Gastrointestinal Disease Is Not Associated With Non-Response to Topical Steroid Treatment in Eosinophilic Esophagitis

S691 Gastroparesis in Patients With Eosinophilic Gastrointestinal Diseases is Associated With Increased Symptoms and Comorbid Conditions

S691 Gastroparesis in Patients With Eosinophilic Gastrointestinal Diseases is Associated With Increased Symptoms and Comorbid Conditions

Successful novel use of dupilumab for gastrointestinal involvement of idiopathic hypereosinophilic syndrome: case report and review of the literature.

Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia leading to organ damage. Gastrointestinal involvement is the third most common manifestation. We present a patient with idiopathic HES with secondary eosinophilic esophagitis (EoE), gastritis, and enteritis, corticosteroids-dependent, azathioprine- and mepolizumab-refractory. The patient achieved clinical and histopathologic remission following dupilumab treatment. A 28year-old female presented with chronic episodic nausea and emesis since childhood and initial diagnosis of primary eosinophilic gastrointestinal disease (EGID), improved with corticosteroids, refractory to azathioprine. She was found to have peripheral eosinophilia and multifactorial anemia, with iron, B12, and folate deficiencies. Esophageal, gastric, duodenal, and terminal ileum biopsies showed significant eosinophilic infiltrate. Bone marrow biopsy at age 31 confirmed HES diagnosis. By age 32, she became total parental nutrition (TPN)-dependent. She failed trials of benralizumab and mepolizumab [anti-interleukin (IL)-5 inhibitors], and cromolyn (mast-cell stabilizer). After developing new esophageal stricture, we initiated dupilumab (IL-4/13 inhibitor), recently FDA-approved for EoE. After 9weeks, esophageal stricture, gut tissue eosinophilia, and prior intestinal ulcerations resolved. She ceased TPN and is tolerating a non-restricted diet, with complete symptom resolution. Our patient's complete remission with dupilumab shows promise for broadening its use in treating GI involvement in HES, along with primary EGIDs.

Quantification of eosinophils in the lower gastrointestinal tract of adults: a review of surgical specimens with normal histology from the Free State province, South Africa.

Eosinophils are normal residents of the gastrointestinal tract (GIT). They are noted in small numbers with significant variation between anatomic locations. An idiopathic increase of eosinophils is known as eosinophilic gastrointestinal disease (EGID). EGIDs are a heterologous group of disorders that produce a range of enteric and colonic syndromes. Their incidence has been increasing worldwide. Our study aimed to quantify eosinophils in each segment of the GIT in surgical specimens with normal histology to facilitate the histological diagnosis of EGID. Similarly, we aimed to describe the effect of race and gender on gastrointestinal eosinophil numbers. A retrospective, quantitative comparative study was performed. We assessed 360 surgical specimens with normal histology from the lower gastrointestinal tract of African and Caucasian adults from the Free State Province, South Africa. The number of eosinophils per mm² was counted. Overall, comparable eosinophil values were noted for both males and females, and African and Caucasian South Africans. However, Caucasians recorded a higher concentration of eosinophils in the appendix and the left colon. Eosinophils were most numerous in the lamina propria, with only small numbers present in the epithelium. Our results show that the South African population has similar eosinophil distribution trends to international studies. However, South Africans had far fewer eosinophils than Japanese and North American adults in each segment. Specific eosinophil reference ranges were formulated to quantify reference ranges of eosinophils in the lower GIT, allowing for the accurate diagnosis of EGIDs in our population in future.

Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.

Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.

Redefining Histological Cell Counts Using a Standardized Method: The Leuven Intestinal Counting Protocol.

The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated, calling for much-needed methodological standardization. We aimed to develop a standardized workflow for duodenal cell quantification and estimate duodenal eosinophil and mast cell numbers in healthy controls. Software-based histological cell quantification using free-sized or fixed-sized regions was developed and applied to digitized hematoxylin and eosin (H&E)-stained slides from 58 individuals (healthy controls [HCs] and patients with functional dyspepsia). Intraclass correlation coefficients (ICCs) compared inter-rater reliability between software-based and microscopic quantification. Reproducibility of the software-based method was validated in an independent cohort of 37 control and functional dyspepsia subjects. Eosinophil identification on H&E staining was compared to immunohistochemistry (IHC). Normal eosinophil (H&E) and mast cell (cKit) ranges were determined in 70 adult HCs. Eosinophil quantification on digitized slides demonstrated excellent (ICC = 0.909) and significantly improved reproducibility over microscopic evaluation (ICC = 0.796, P = 0.0014), validated in an independent cohort (ICC = 0.910). Duodenal eosinophils were more abundant around crypts than in villi ( P < 0.0001), while counts were similar on matched H&E- and IHC-stained slides ( P = 0.55). Mean ± SD (95th percentile) duodenal eosinophils and mast cells in HC were 228.8/mm 2 ± 94.7 (402.8/mm 2 ) and 419.5/mm 2 ± 132.2 (707.6/mm 2 ), respectively. We developed and validated a standardized approach to duodenal histological cell quantification, generalizable to various mucosal cell types. Implementation of software-based quantification identified 400 eosinophils/mm 2 and 700 mast cells/mm 2 as thresholds for abnormal duodenal infiltration.

Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis

BackgroundBecause young children cannot self-report symptoms, there is a need for parent surrogate reports. While early work suggested parent child alignment for eosinophil esophagitis (EoE) patient reported outcomes (PROs), the longitudinal alignment is unclear. ObjectiveTo assess the agreement and longitudinal stability of PROs between children with EoE and their parents. Methods292 parent-child respondents completed 723 completed questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. ResultsThe cohort had a median disease duration equalling 3.7 years and was predominantly male (73.6%) and white (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent report (PEESSv2.0 0.83, PedsQL-EoE 0.74) with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (p ≥ 0.32), whereas child-reported PedsQL-EoE scores improved (p = 0.026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (p < 0.001) and differences were driven by psychosocial PRO domains. ConclusionThere is strong longitudinal alignment between child and parent report using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

Eosinophilic Gastrointestinal Disease Presenting as Chronic Diarrhea: A Case Report

Eosinophilic Gastrointestinal Disease Presenting as Chronic Diarrhea: A Case Report

Diagnosis and management of eosinophilic esophagitis in children: An update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and histologically by predominantly eosinophilic infiltration of the squamous epithelium. European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) published a guideline in 2014; however, the rapid evolution of knowledge about pathophysiology, diagnostic criteria, and therapeutic options have made an update necessary. A consensus group of pediatric gastroenterologists from the ESPGHAN Working Group on Eosinophilic Gastrointestinal Diseases (ESPGHAN EGID WG) reviewed the recent literature and proposed statements and recommendations on 28 relevant questions about EoE. A comprehensive electronic literature search was performed in MEDLINE, EMBASE, and Cochrane databases from 2014 to 2022. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence and formulate recommendations. A total of 52 statements based on the available evidence and 44 consensus-based recommendations are available. A revision of the diagnostic protocol, options for initial drug treatment, and the new concept of simplified empiric elimination diets are now available. Biologics are becoming a part of the potential armamentarium for refractory EoE, and systemic steroids may be considered as the initial treatment for esophageal strictures before esophageal dilation. The importance and assessment of quality of life and a planned transition to adult medical care are new areas addressed in this guideline. Research in recent years has led to a better understanding of childhood EoE. This guideline incorporates the new findings and provides a practical guide for clinicians treating children diagnosed with EoE.

Eosinophilic gastrointestinal diseases: current perspectives on pathogenesis and management

Eosinophilic gastrointestinal diseases: current perspectives on pathogenesis and management

The Natural History of Eosinophilic Gastrointestinal Diseases Is Influenced by Age of Onset and Location of Involvement.

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.

Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review

Abstract Introduction Eosinophilic gastrointestinal diseases (EGIDs) are rare and heterogeneous diseases characterized by excessive eosinophilic infiltration of the digestive system. D-dimer levels and its possible association with disease course were not reported. Case series We reported a series of three EGID cases presenting with high levels of D-dimer. No evidence for potential venous thromboembolism was found through computed tomography pulmonary angiogram and vascular ultrasounds. Moreover, D-dimer levels decreased after short-time systemic prednisolone administration, accompanied by remission of clinical symptoms and decrease of peripheral eosinophil counts and IgE levels. Conclusion Elevation of D-dimer in EGID may not represent thrombotic events but is possibly associated with disease severity. More population-based studies are needed to delineate the potential relationship among D-dimer, thrombosis, and inflammation in EGID.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis

The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P< .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P< .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r= -0.352, P< .001) and both inflammatory and fibrostenotic features scores (r= -0.665, P< .001; r= -0.446, P< .001, respectively), but not with symptoms and complications scores (r= 0.047, P= .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Host-related low-prevalence gastritides: Epidemiological and clinical characterization

IntroductionA recent consensus meeting (RE.GA.IN) addressed “host-related, low-prevalence gastritis”: eosinophilic (EoG), lymphocytic (Hp-pos_LyG and Hp-neg_LyG), collagenous (CollG), and granulomatous gastritis (GrG). Our study evaluates their clinico-epidemiological characteristics. Materials and MethodsWe extracted all patients with a diagnosis of EoG, LyG, CollG, and GrG from a clinicopathological database and compared their demographics, clinical and endoscopic characteristics, associated conditions, and clinical awareness to those of all other subjects in the database (controls). ResultsThere were 1,781,005 unique patients (median age 57 years; 55.7 % female). Hispanics were overrepresented amongst those with Hp-pos_LyG. Subjects with GrG had a high prevalence of erosions and ulcers. Clinical awareness of these conditions was dismal (<1:10,000 patients). Some clinical manifestations were more common in patients with certain gastritides (e.g., vomiting and diarrhea in CollG; anemia in LyG), but none were sufficiently distinctive to suggest a clinical diagnosis. EoG was associated with EoE; LyG had a strong association with celiac disease; CollG with microscopic colitis; and GrG with Crohn disease. ConclusionsThe diagnosis of these gastritides (between <1: in 1,000 and 1 in 5000 subjects) rests on histopathology. They remain poorly characterized and clinically neglected. Yet, their associations may herald other conditions: eosinophilic gastrointestinal diseases (EGID), celiac, and Crohn disease. Patients might benefit from increased detection and characterization.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis

BackgroundThe mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. ObjectiveWe examined the correlation of a validated, patient-reported outcome (PRO) metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. MethodsData were extracted from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Patients were subgrouped by esophageal dilation history. We compared a validated PRO metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We utilized single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. ResultsThe EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31, P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3, P < .05). Of these, 11 were expressed in non-epithelial cells and 3 in epithelial cells; during histologic remission, only 4/11 (36%) non-epithelial versus 3/3 (100%) epithelial genes had decreased expression to <50% of that in active EoE. Fibroblasts expressed 5/11 (45%) non-epithelial EEsAI-associated EDP genes. A subset of non-epithelial (8/11, 73%), but not EoE-representative (0/4, 0%; CCL26, CAPN14, DSG1, SPINK7), genes was upregulated in patients with EoE with the highest versus lowest symptom burden. ConclusionThe correlation of symptoms and non-epithelial esophageal gene expression substantiates that non-epithelial cells (e.g., fibroblasts) likely contribute to symptom severity.

Challenging assumptions about the demographics of eosinophilic gastrointestinal diseases: A systematic review

BackgroundThe demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis. ObjectivesWe aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics. MethodsWe conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index (BMI), insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed using Chi-squared tests. Demographic reporting was compared to recent guidelines. ResultsAmong 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race [n=4], ethnicity [n=1], insurance [n=1]) or not described (BMI, urban/rural residence). A higher proportion of males was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. Sex and gender were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines. ConclusionCurrent data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs.

Dupilumab in adolescent eosinophilic esophagitis: Experience with fibrostenosis and EGID with esophageal involvement.

We evaluated patients aged 12-20 on dupilumab 300 mg weekly for treatment of eosinophilic esophagitis (EoE) who had ≥1 follow-up endoscopy at a tertiary care pediatric hospital (n = 18). Fifty percent had inflammatory EoE (n = 9), 22% had fibrostenotic EoE (n = 4), and 28% had non-EoE eosinophilic gastrointestinal disease (EGID) with esophageal involvement (n = 5). Ninety-four percent discontinued topical corticosteroids (TCS) 2-4 weeks after starting dupilumab. Eighty-nine percent of inflammatory EoE patients had histological response (<15 eosinophils/high-powered field) after an average of 19.1 weeks. One hundred percent of patients with fibrostenotic disease exhibited histological response after 16.8 weeks. Of patients with non-EoE EGID, 60% achieved esophageal histological response after an average of 40.1 weeks. In a small cohort, dupilumab was very effective for adolescent inflammatory and fibrostenotic EoE despite rapid weaning of TCS. Dupilumab was also somewhat effective for non-EoE EGID with esophageal involvement; however, a longer duration of therapy was required.

Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

Prevalence of eosinophilic gastrointestinal diseases in children with short bowel syndrome: A single center study.

Patients with short bowel syndrome (SBS) have multiple risk factors for eosinophilic gastrointestinal diseases (EGIDs) including increased risk for intestinal dysbiosis and food allergy compared to their counterparts with normal anatomy. However, there is limited data on the prevalence of EGIDs in children with SBS. We aimed to define the prevalence of EGIDs in an SBS cohort and its association with different risk factors via a retrospective chart review of patients with SBSat Children's National Hospital. The prevalence of eosinophilic esophagitis in our SBS cohort was 10%, eosinophilic gastritis was 4.9%, and eosinophilic enteritis was 4.9%. SBS patients with history of allergy or atopy were more likely to have esophageal and intestinal eosinophilia on biopsy than patients without allergy. The prevalence of EGIDs in our SBS cohort is significantly higher than in the general population and may be associated with allergic polarization.