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BACKGROUND: Intraepithelial mast cells (MC) are increased in Eosinophilic Esophagitis (EoE) and reduced with elimination of dietary antigens. Single food reintroduction can identify triggers of eosinophilia however it remains unknown the extent to which specific foods trigger intraepithelial mastocytosis. We hypothesized that specific foods drive different degrees of MC inflammation. METHODS: We previously reported a prospective pediatric EoE cohort treated with a 4-food elimination diet (4FED) with removal of soy, egg, wheat, milk. We retrieved unstained slides in which baseline, 4FED, and post-4FED diet reintroduction time points were available. Slides were stained with tryptase, and intraepithelial MCs were counted. Comparisons were made by stratifying patients by eosinophilia, basal cell hyperplasia (BCH), endoscopic abnormalities, and symptoms. Pearson correlation was assessed for MCs with eosinophilic, endoscopic and BCH severity, symptoms, and a novel mucosal activity score (MAS) combining endoscopic and histologic structural severity. RESULTS: Slides were available from 37 patients with at least 1 food reintroduced. MCs were significantly reduced with 4FED. Wheat led to increased intraepithelial MCs in the upper esophagus and with food-induced eosinophilia, while milk led to significantly increased MCs in the upper and lower esophagus and was significantly associated with patients with food-triggered eosinophilia, endoscopic abnormalities, BCH, and symptoms. MCs best correlated with the MAS during milk reintroduction. CONCLUSION: In children with EoE, MCs are reduced with 4FED. During milk reintroduction, significant increases in MCs were observed with all metrics of inflammation along with moderate correlation with structural mucosal activity that was not seen with other foods. This suggests milk exerts unique effects either directly or indirectly on MCs in the esophagus in EoE patients.
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The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 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. RESULTS: The cohort had a median disease duration equaling 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 reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.
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BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: 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. RESULTS: 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. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.
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Esofagitis Eosinofílica , Índice de Severidad de la Enfermedad , Humanos , Esofagitis Eosinofílica/diagnóstico , Masculino , Femenino , Niño , Adulto , Adolescente , Preescolar , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. OBJECTIVE: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. METHODS: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome 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 used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. RESULTS: The 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 nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden. CONCLUSION: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.
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Mast cells play a central role in the pathogenesis of eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis. Their interactions with immune and structural cells, involvement in tissue remodeling, and contribution to symptoms make them attractive targets for therapeutic intervention. More is being discovered regarding the intricate interplay of mast cells and eosinophils. Recent studies demonstrating that depletion of eosinophils is insufficient to improve symptoms of EGIDs have raised the question of whether other cells may play a role in symptomatology and pathogenesis of EGIDs.
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Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Mastocitos , Enteritis/terapia , Enteritis/diagnóstico , Gastritis/diagnóstico , Gastritis/terapia , Esofagitis Eosinofílica/terapia , Esofagitis Eosinofílica/diagnósticoRESUMEN
The pathophysiology of mast cell (MC)-driven disorders is diverse, ranging from localized reactions to systemic disorders caused by abnormal accumulation and activation in multiorgan systems. Prompt and accurate diagnosis is critically important, both for informing treatment and objective assessment of treatment outcomes. As new therapeutics are being developed to deplete MCs or silence them (eg, by engaging inhibitory receptors that block activation), new biomarkers are needed that can distinguish between MC activation versus burden. Serum tryptase is the gold standard for assessing both MC burden and activation; however, commercial tryptase assays have limitations related to timing of release, lack of discernment between inactive (α) and active (ß) forms of tryptase, and interpatient variability of baseline levels. Alternative approaches to measuring MC activation include urinary MC mediators, flow cytometry-based assays or gene expression profiling. Additional markers of MC activation are needed for use in clinical diagnostics, to help selection of treatment of MC diseases, and for assessing outcomes of therapy. We review the spectrum of disorders with known or suspected MC contribution, describe the utility and limitations of current MC markers and assays, and discuss the need for new markers that can differentiate between MC activation and burden.
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Biomarcadores , Mastocitos , Humanos , Mastocitos/inmunología , Triptasas/sangre , Recuento de Células , Mastocitosis/diagnóstico , AnimalesRESUMEN
CONTEXT.: Mast cells are essential components of the immune system and play crucial pathogenetic roles in several digestive diseases, including mastocytic enterocolitis and eosinophilic gastrointestinal disorders. Pathologists have rarely been asked to evaluate the distribution and density of mast cells in gastrointestinal (GI) biopsy specimens. However, such requests are becoming more common because of an increasing awareness of the role of mast cells in functional GI disease and in both esophageal and nonesophageal eosinophilic gastrointestinal disorders. OBJECTIVE.: To provide pathologists with tools to incorporate the assessment of mast cells in the evaluation of esophageal, gastric, and intestinal specimens by developing a systematic approach to their evaluation, counting, and reporting. DESIGN.: This study consisted of a review of the literature followed by multiple consensus sessions to decide where to count mast cells and what a countable mast cell is. RESULTS.: We reviewed 135 papers addressing the content of mast cells in the digestive tract, selected 21 that detailed how cells were counted (microscope lens, area of high-power fields, locations evaluated, type of cells considered as countable), and summarized their data in a table. Then, drawing from both the acceptable literature and our own extensive experience, we reached a tentative consensus on: (1) the normal numbers in the different segments of the GI tract; (2) the morphology of countable mast cells; and (3) the locations and strategies for counting them. CONCLUSIONS.: The result is a set of suggestions for reporting mast cell counts, their distribution, and their location in a way clinicians can understand and use for management decisions.
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Enfermedades Gastrointestinales , Mastocitosis , Humanos , Mastocitos/patología , Patólogos , Tracto Gastrointestinal/patología , Mastocitosis/diagnóstico , Mastocitosis/patología , Enfermedades Gastrointestinales/patologíaRESUMEN
The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs.
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Asma , Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Estados Unidos , Enteritis/diagnóstico , Enteritis/terapia , Asma/diagnóstico , Asma/terapiaRESUMEN
In response to the social inequities that exist in health care, the NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee to examine systemic racism and implicit bias in the care and research of eosinophilic gastrointestinal diseases (EGIDs). Herein, we describe our process, highlighting milestones and issues addressed since the committee's inception, which we hope will inspire other researchers to enhance diversity, equity, inclusion, and accessibility (DEIA) in their fields. Our journey began by establishing mission and vision statements to define the purpose of the committee. Regular discussion of diversity-related topics was incorporated into existing meetings and web-based materials were shared. This was followed by educational initiatives, including establishing a library of relevant publications and a speaker series to address DEIA topics. We then established a research agenda focused on the following actionable items: (1) to define what is known about the demographics of EGIDs by systematic review of population-based studies; (2) to develop a practical tool for reporting participant demographics to reduce bias in EGID literature; (3) to examine health disparities in the care of individuals with eosinophilic esophagitis who present to the emergency department with an esophageal food impaction; (4) to examine how access to a gastroenterologist affects the conclusions of published research examining the prevalence of pediatric eosinophilic esophagitis; and (5) to develop a model for examining the dimensions of diversity, and provide a framework for CEGIR's ongoing projects and data capture. In addition to promoting consciousness of DEIA, this initiative has fostered inclusivity among CEGIR members and will continue to inspire positive changes in EGID care and research.
Diversity in Eosinophilic Gastrointestinal Disease Research To address systemic bias in patient care and research in eosinophilic gastrointestinal diseases, the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) recently formed a diversity committee. The CEGIR diversity committee has defined its purpose through mission and vision statements and developed structured educational and research initiatives to enhance diversity, equity, inclusivity, and accessibility (DEIA) in all CEGIR activities. Here, we share the process of formation of our diversity committee, highlighting milestones achieved and summarizing future directions. We hope that this report will serve as a guide and an inspiration for other researchers to enhance DEIA in their fields.
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Macrophages (MΦ) play a role in neonatal etiologies of obstructive cholestasis, however, the role for precise MΦ subsets remains poorly defined. We developed a neonatal murine model of bile duct ligation (BDL) to characterize etiology-specific differences in neonatal cholestatic MΦ polarization. Neonatal BDL surgery was performed on female BALB/c mice at 10 days of life (DOL) with sham laparotomy as controls. Comparison was made to the Rhesus Rotavirus (RRV)-induced murine model of biliary atresia (BA). Evaluation of changes at day 7 after surgery (BDL and sham groups) and murine BA (DOL14) included laboratory data, histology (H&E, anti-CD45 and anti-CK19 staining), flow cytometry of MΦ subsets by MHCII and Ly6c expression, and single cell RNA-sequencing (scRNA-seq) analysis. Neonatal BDL achieved a 90% survival rate; mice had elevated bile acids, bilirubin, and alanine aminotransferase (ALT) versus controls (p < 0.05 for all). Histology demonstrated hepatocellular injury, CD45+ portal infiltrate, and CK19+ bile duct proliferation in neonatal BDL. Comparison to murine BA showed increased ALT in neonatal BDL despite no difference in histology Ishak score. Neonatal BDL had significantly lower MHCII-Ly6c+ MΦ versus murine BA, however, scRNA-seq identified greater etiology-specific MΦ heterogeneity with increased endocytosis in neonatal BDL MΦ versus cellular killing in murine BA MΦ. We generated an innovative murine model of neonatal obstructive cholestasis with low mortality. This model enabled comparison to murine BA to define etiology-specific cholestatic MΦ function. Further comparisons to human data may enable development of immune modulatory therapies to improve patient outcomes.
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Atresia Biliar , Colestasis , Humanos , Femenino , Animales , Ratones , Modelos Animales de Enfermedad , Conductos Biliares/cirugía , Alanina TransaminasaRESUMEN
BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.
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Esofagitis Eosinofílica , Humanos , Niño , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/genética , Alimentos/efectos adversos , Alérgenos , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
We investigated reproducibility and generalizability of the recently developed web-based model to predict lamina propria fibrosis (LPF) in esophageal biopsies with inadequate lamina propria (LP) from patients with eosinophilic esophagitis (EoE) using an independent dataset (N = 183). For grade and stage scores of LPF, the area under the curve for predictive model was 0.77 (0.69-0.84) and 0.75 (0.67-0.82), and its accuracy was 78% and 72%, respectively. These model performance metrics were similar to that of the original model. A significant positive correlation was noted between the models' predictive probability and the grade and stage of LPF assessed by a pathologist (grade: r2 = 0.48, P < 0.001; and stage: r2 = 0.39, P < 0.001). These results support the reproducibility and generalizability of the web-based model to predict the presence of LPF in esophageal biopsies with inadequate LP in EoE. Additional studies are warranted to refine the web-based predictive models to provide predictive probability for sub-scores of LPF severity.
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Esofagitis Eosinofílica , Humanos , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/patología , Reproducibilidad de los Resultados , Membrana Mucosa , Fibrosis , InternetRESUMEN
BACKGROUND & AIMS: The nature of the involvement of esophageal tissue in eosinophilic esophagitis (EoE) is unclear. We estimated the intrabiopsy site agreements of the EoE Histologic Scoring System (EoEHSS) scores for the grade (degree) and stage (extent) of involvement of the esophageal epithelial and lamina propria and examined if the EoE activity status influenced the intrabiopsy site agreement. METHODS: Demographic, clinical, and EoEHSS scores collected as part of the prospective Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages study were analyzed. A weighted Cohen's kappa agreement coefficient (k) was used to calculate the pairwise agreements for proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites, separately for grade and stage scores, for each of the 8 components of EoEHSS. A k > 0.75 was considered uniform involvement. Inactive EoE was defined as fewer than 15 eosinophils per high-powered field. RESULTS: EoEHSS scores from 1263 esophageal biopsy specimens were analyzed. The k for the stage of involvement of the dilated intercellular spaces across all 3 sites in inactive EoE was consistently greater than 0.75 (range, 0.87-0.99). The k for lamina propria fibrosis was greater than 0.75 across some of the biopsy sites but not across all 3. Otherwise, the k for all other features, for both grade and stage, irrespective of the disease activity status, was 0.75 or less (range, 0.00-0.74). CONCLUSIONS: Except for the extent of involvement of dilated intercellular spaces in inactive EoE, the remaining epithelial features and lamina propria are involved unevenly across biopsy sites in EoE, irrespective of the disease activity status. This study enhances our understanding of the effects of EoE on esophageal tissue pathology.
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Esofagitis Eosinofílica , Humanos , Esofagitis Eosinofílica/patología , Estudios Prospectivos , Membrana Mucosa/patología , Eosinófilos/patología , Biopsia , Epitelio/patologíaRESUMEN
INTRODUCTION: Chronic graft failure (CGF) is the leading cause of mortality in pediatric heart transplant (PHT) patients and has multifactorial pathogenesis including cardiac allograft vasculopathy (CAV). CGF can present with microvessel disease (MVD) and myocardial fibrosis on endomyocardial biopsies (EMB). We investigated if CGF due to moderate- severe (M-S) CAV has histopathologic MVD and fibrosis prior to or at the time of CAV diagnosis. METHOD: This retrospective case-control study included PHT with CGF secondary to M-S CAV. Control patients had no CAV or CGF. EMBs from CAV (3 sets: at 1-year post-transplant 1yrCAV, pre-CAV, and at the time of CAV diagnosis) and non-CAV cohorts were reviewed to grade the fibrosis and quantify MVD. Histopathologic changes were correlated and compared between CAV/non-CAV groups. RESULTS: Each group had 8 patients. The median age at transplantation and time since transplant were similar between the two groups (P=.71 and P=.91, respectively). Fibrosis grade was 3.0 for CAV cohort compared to 1.0 for control (P= .003) and MVD score was 2.1 in CAV and 0.5 in non-CAV patients (P=.003). Similar degrees of fibrosis and MVD were present even before any evidence of CAV (1yrCAV fibrosis grade 2.5, pre-CAV fibrosis grade 2; 1yrCAV vs CAV P=.75, pre-CAV vs CAV P=.63; 1yrCAV MVD score 2, pre-CAV MVD score 2; 1yrCAV vs CAV P=1, pre-CAV vs CAV P=.91). The degree of MVD correlated with fibrosis (r=0.63, P<.0001) for all EMBs. CONCLUSION: Simultaneous myocardial fibrosis and MVD are noted in CGF secondary to M-S CAV, changes that occur before angiographic CAV. EMBs can reveal significant changes in patients with subsequent development of CAV and may be used to modify the follow-up and treatment for these high-risk patients.
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Trasplante de Corazón , Humanos , Niño , Estudios Retrospectivos , Estudios de Casos y Controles , Trasplante de Corazón/efectos adversos , Microvasos , Fibrosis , Aloinjertos , Biopsia , Rechazo de Injerto/etiología , Angiografía CoronariaRESUMEN
OBJECTIVE: To assess hepatic transcriptional signatures in infants with gestational alloimmune liver disease (GALD) compared with other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF. STUDY DESIGN: Neonates with ALF (international normalized ratio ≥2 within 30 days of life) and deceased neonates without liver disease (<30 days of age) with available liver tissue between 2010 and 2021 were identified at Ann & Robert H. Lurie Children's Hospital of Chicago. Clinical information, liver histology, and data from RNA-sequencing analysis was compared between neonates with GALD, non-GALD etiologies of neonatal ALF, and nondiseased neonatal liver. RESULTS: Quantification of trichrome staining showed an increase in fibrosis in patients with GALD vs those with non-GALD neonatal ALF (P = .012); however, quantification of α-cytokeratin 19-positive ductules did not differ between groups (P = .244). Gene set enrichment analysis of RNA-sequencing data identified the pathways of complement activation, fibrosis, and organogenesis to be upregulated in patients with GALD with ALF. In contrast, patients with non-GALD causes of neonatal ALF had increased gene expression for interferon-driven immune pathways. Individual genes upregulated in GALD included matrix metallopeptidase 7, hepatocyte growth factor, and chemokine ligand 14. CONCLUSIONS: We have identified distinct pathways that are significantly upregulated in patients with GALD and potential disease-specific diagnostic biomarkers. Future studies will aim to validate these findings and help identify GALD-specific diagnostic biomarkers to improve diagnostic accuracy and reduce GALD-associated patient mortality.
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Fallo Hepático Agudo , Lactante , Recién Nacido , Humanos , Niño , Fallo Hepático Agudo/genética , Fibrosis , Biomarcadores/análisis , ChicagoRESUMEN
BACKGROUND & AIMS: Identification of fibrosis in pediatric eosinophilic esophagitis (EoE) relies on symptom assessment and endoscopy. Symptoms are highly variable, and early fibrotic remodeling may go undetected on endoscopy yet contribute to esophageal dysfunction. We aimed to assess whether esophageal distensibility has utility in defining fibrostenotic severity in a cohort of pediatric patients with EoE with symptoms of esophageal dysfunction. METHODS: We analyzed a prospectively recruited a cohort of children ages 9 to 21 years undergoing upper endoscopy and Endoscopic Functional Lumen Imaging Probe (EndoFLIP) for suspected or previously diagnosed EoE. Esophageal distensibility was evaluated by the distensibility index (DI) and esophageal diameter at the distensibility plateau. The association of esophageal distensibility to clinical, endoscopic, and histologic parameters of disease severity was assessed. Receiver operating characteristic analysis was performed to determine the utility of distensibility in defining esophageal rigidity in pediatric EoE. RESULTS: We identified 59 pediatric patients with EoE undergoing endoscopy and EndoFLIP at a single pediatric tertiary referral center. DI (mm2/mmHg) was significantly lower in patients with fibrotic as compared with inflammatory features on endoscopy (median, 3.3; interquartile range, 2.3-4.4) vs median, 5.5; interquartile range, 4.1-6.0; P = .02) and showed no correlation with eosinophil count. DI <4.5 mm2/mmHg predicted grade 2 rings on endoscopy with area under the curve of 0.81 (P = .0004). DI predicted food impaction in both unadjusted and adjusted models (fully adjusted odds ratio, 1.44; 95% confidence interval, 1.02-2.14; P = .0486). CONCLUSION: Esophageal distensibility determined by EndoFLIP is a measure of fibrostenotic severity that can be used to clinically phenotype pediatric EoE. We propose parameters of DI <4.5 mm2/mmHg for defining esophageal rigidity in pediatric patients with EoE ages 9 years and older.
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Esofagitis Eosinofílica , Humanos , Esofagitis Eosinofílica/patología , Endoscopía Gastrointestinal , FibrosisRESUMEN
OBJECTIVE: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. METHODS: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. RESULTS: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. CONCLUSIONS: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.
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Esofagitis Eosinofílica , Microbiota , Adulto , Humanos , Niño , Esofagitis Eosinofílica/patología , Estudios ProspectivosRESUMEN
Esophagogastroduodenoscopy (EGD) is a frequently utilized investigative tool in the management of gastrointestinal conditions in children. Biopsies obtained during EGD may pose risk for post-operative adverse events (AEs), and further understanding of risk is imperative to provide informed consent to families and safe patient care. In particular, the impact of biopsy number and location on the development of AEs has not been studied in pediatric patients. We prospectively assessed for AEs by telephone survey 3-7 days after 209 EGDs performed on patients ages 1-21 years over a 1-year period. Demographic, endoscopic, and histologic data were collected. The most common symptoms reported were throat pain (61%), chest pain (26%), and dysphagia (26%). Binary regression models identified age and pre-operative symptoms as factors that influenced the likelihood of post-operative morbidity. Multiple biopsies from 3 different locations of the esophagus did not impact the risk of post-operative AEs.