Eosinophilic gastrointestinal disorders (EGID)

doi:10.1016/j.jaci.2003.10.047

Journal of Allergy and Clinical Immunology

Volume 113, Issue 1, January 2004, Pages 11-28

https://doi.org/10.1016/j.jaci.2003.10.047 Get rights and content

Abstract

Primary eosinophilic gastrointestinal disorders are defined as disorders that selectively affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (eg, drug reactions, parasitic infections, and malignancy). These disorders include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis and are occurring with increasing frequency. Significant progress has been made in elucidating that eosinophils are integral members of the gastrointestinal mucosal immune system and that eosinophilic gastrointestinal disorders are primarily polygenic allergic disorders that involve mechanisms that fall between pure IgE-mediated and delayed T_H2-type responses. Preclinical studies have identified a contributory role for the cytokine IL-5 and the eotaxin chemokines, providing a rationale for specific disease therapy. An essential question is to determine the cellular and molecular basis for each of these clinical problems and the best treatment regimen, which is the main subject of this review.

Section snippets

Overview of eosinophilic gastrointestinal disorders

Eosinophil accumulation in the gastrointestinal tract is a common feature of numerous gastrointestinal disorders, including classic IgE-mediated food allergy,1, 2 eosinophilic gastroenteritis,3, 4 allergic colitis,5, 6, 7 eosinophilic esophagitis (EE),8, 9, 10 inflammatory bowel disease (IBD),11, 12, 13 and gastroesophageal reflux disease (GERD).14, 15, 16, 17, 18 In IBD eosinophils usually represent only a small percentage of the infiltrating leukocytes,11, 19 but their level has been proposed

Eosinophil growth and development

The eosinophil is formed in the bone marrow, where it spends about 8 days maturing under the regulation of the transcription factors GATA-1, GATA-2, and c/EBP (Fig 2).40, 41, 42 Notably, GATA-1 and GATA-2 overexpression are sufficient signals for promoting eosinophil development in avian, murine, and human systems. Additionally, mice with a targeted genetic deletion in the high-affinity GATA site present in the GATA-1 promoter are selectively deficient in the eosinophil lineage.⁴¹ These

Regulation of eosinophil tissue accumulation

Numerous inflammatory mediators have been implicated in regulating eosinophil accumulation, including IL-1, IL-3, IL-4, IL-5, IL-13, and GM-CSF and the chemokines RANTES, monocyte chemoattractant protein (MCP) 3, MCP-4, macrophage inflammatory protein 1α, and eotaxin 1, eotaxin 2, and eotaxin 3.44, 50, 51 IL-3 and GM-CSF, in association with IL-5, enhance eosinophil development, migration, and effector function, whereas IL-1, IL-4, IL-13, and TNF-α regulate eosinophil trafficking by promoting

Eotaxin subfamily of chemokines

Eotaxin was initially discovered by using a biologic assay in guinea pigs designed to identify the molecules responsible for allergen-induced eosinophil accumulation in the lungs.⁵³ A partial amino acid sequence facilitated the genetic cloning of the genes and cDNA for guinea pig, murine, and human eotaxin, which led to the identification of eotaxin as a member of the CC chemokine family most homologous to the MCP subfamily,72, 73, 74, 75, 76 all being present in the same genetic locus (human

Constitutive gastrointestinal eosinophils

Eosinophils have been noted to be present at low levels in numerous tissues. When a large series of biopsy and autopsy specimens were analyzed, the only organs that demonstrated tissue eosinophils (at substantial levels) were the gastrointestinal tract, spleen, lymph nodes, and thymus (Fig 2).¹¹⁰ Interestingly, eosinophil infiltrations were only associated with eosinophil degranulation in the gastrointestinal tract. Examination of eosinophils throughout the gastrointestinal tracts of

Role of baseline eosinophils

The beneficial function of eosinophils has been primarily attributed to their ability to defend the host against parasitic helminths. This is based on several lines of evidence, including (1) the ability of eosinophils to mediate antibody-dependent (or complement-dependent) cellular toxicity against helminths in vitro,111, 112 (2) the observation that eosinophil levels increase during helminth infections and that eosinophils aggregate and degranulate in the local vicinity of damaged parasites

Pro-inflammatory role of eosinophils in EGIDs

Eosinophils are pleiotropic cells stimulated by a variety of triggers (Fig 3). In vitro studies have shown that eosinophil granule constituents are toxic to a variety of tissues, including intestinal epithelium.¹²⁵ Eosinophil granules contain a crystalloid core composed of major basic protein (MBP) 1 (and MBP-2) and a matrix composed of eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase (EPO; Fig 3).¹²⁶ These cationic proteins share certain

Clinical evaluation for EGIDs

Patients with EGIDs present with a variety of clinical problems, most commonly failure to thrive, abdominal pain, irritability, gastric dysmotility, vomiting, diarrhea, dysphagia, microcytic anemia, and hypoproteinemia.²¹ A diagnostic evaluation for EGIDs should be performed on all patients with these refractory problems, especially in individuals with a strong history of allergic diseases, peripheral blood eosinophilia, and/or a family history of EGIDs (Table I). Depending on the intestinal

Evaluation for HES in patients with apparent EGIDs

The term HES was introduced by Anderson and Hardy¹⁴³ in 1968 to designate patients with marked eosinophilia. They reported 3 patients, all men between the ages of 34 and 47, who had cardiopulmonary symptoms, fever, sweats, weight loss, and marked eosinophilia. Two of the patients died, and at autopsy, their hearts were enlarged and showed mural thrombi. Chusid and associates¹⁴⁴ formulated the diagnostic criteria for HES to include (1) persistent eosinophilia of at least 1500 cells/mm² for a

Eosinophilic esophagitis

The esophagus is normally devoid of eosinophils, and therefore the finding of esophageal eosinophils denotes pathology.9, 10 It is now appreciated that many disorders are accompanied by eosinophil infiltration in the esophagus, such as EE, eosinophilic gastroenteritis, GERD, recurrent vomiting, parasitic and fungal infections, IBD, HES, esophageal leiomyomatosis, myeloproliferative disorders, carcinomatosis, periarteritis, allergic vasculitis, scleroderma, and drug injury.10, 156

Eosinophilic gastritis and gastroenteritis

In contrast to the esophagus, the stomach and intestine have readily detectable baseline eosinophils under healthy conditions. As such, the diagnosis of eosinophilic gastritis, enteritis, and gastroenteritis is even more complex than EE. In this review, eosinophilic gastritis, enteritis, and gastroenteritis are grouped together because they are clinically similar and because there is a paucity of information available concerning their pathogenesis; however, it is likely that they are indeed

Eosinophilic colitis

Eosinophils accumulate in the colons of patients with a variety of disorders, including eosinophilic gastroenteritis, allergic colitis of infancy, infections (including pinworms and dog hookworms), drug reactions, vasculitis (eg, Churg-Strauss syndrome), and IBD.43, 44, 45, 46, 48, 110, 111, 181, 182 Allergic colitis in infancy (also known as dietary protein–induced proctocolitis of infancy syndrome) is the most common cause of bloody stools in the first year of life.183, 184 Similar to other

Summary and concluding remarks

In this article we have reviewed the basic properties of eosinophils, their regulation and role in healthy states, and the pathogenesis and treatment of EGIDs (Fig 4). In brief, under baseline healthy conditions, eosinophils normally account for a small subset of circulating blood cells and primarily reside in the gastrointestinal tract and hematopoietic organs. Their production is tightly regulated by the transcription factors GATA-1, GATA-2, and c/EBP, which instruct the hematopoietic

Acknowledgments

I thank the numerous colleagues who have contributed to the body of information presented in this review, including Drs Simon Hogan, Anil Mishra, Phil Putnam, Amal Assa'ad, Margaret Collins, Eric Brandt, Nives Zimmermann, Paul Foster, Jesus Guajardo, Richard Noel, Mitch Cohen, Glenn Furuta, and Ha Shem. I also thank Dr Troy Scribner for the initial draft of the cover illustration and Andrea Lippelman and Joy Rothenberg.

References (189)

A Keshavarzian et al.
Activated eosinophils in familial eosinophilic gastroenteritis
Gastroenterology
(1985)
MP Sherman et al.
Neonatal eosinophilic colitis
J Pediatr
(1982)
RD Odze et al.
Allergic colitis in infants
J Pediatr
(1995)
VL Fox et al.
Eosinophilic esophagitis: It's not just kid's stuff
Gastrointest Endosc
(2002)
ME Rothenberg et al.
Pathogenesis and clinical features of eosinophilic esophagitis
J Allergy Clin Immunol
(2001)
HS Winter et al.
Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis
Gastroenterology
(1982)
ME Rothenberg et al.
Gastrointestinal eosinophils in health and disease
Adv Immunol
(2001)
P Desreumaux et al.
Activated eosinophils in inflammatory bowel disease: do they matter?
Am J Gastroenterol
(1999)
JR Guajardo et al.
Eosinophil-associated gastrointestinal disorders: a world-wide-web based registry
J Pediatr
(2002)
JM Spergel et al.
The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis
J Allergy Clin Immunol
(2002)

KJ Kelly et al.

Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula

Gastroenterology

(1995)

SC Bischoff

Mucosa allergy: role of mast cells and eosinophil granulocytes in the gut

Baillieres Clin Gastroenterol

(1996)

HA Sampson

Food allergy. Part 1: immunopathogenesis and clinical disorders

J Allergy Clin Immunol

(1999)

PF Weller

The idiopathic hypereosinophilic syndrome

Blood

(1994)

AJ Wardlaw

Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm

J Allergy Clin Immunol

(1999)

DS Silberstein

Eosinophil function in health and disease

Crit Rev Oncol Hematol

(1995)

BS Bochner

Road signs guiding leukocytes along the inflammation superhighway

J Allergy Clin Immunol

(2000)

SK Shaw et al.

The beta 7 integrins in mucosal homing and retention

Semin Immunol

(1995)

EC Butcher et al.

Lymphocyte trafficking and regional immunity

Adv Immunol

(1999)

WJ Sandborn et al.

Biologic therapy of inflammatory bowel disease

Gastroenterology

(2002)

A Mishra et al.

Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking

J Biol Chem

(2002)

H Floyd et al.

Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily

J Biol Chem

(2000)

KK Kikly et al.

Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils

J Allergy Clin Immunol

(2000)

M Kitaura et al.

Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3

J Biol Chem

(1999)

H Nomiyama et al.

Assignment of the human CC chemokine MPIF-2/eotaxin-2 (SCYA24) to chromosome 7q11.23

Genomics

(1998)

C Combadiere et al.

Cloning and functional expression of a human eosinophil CC chemokine receptor

J Biol Chem

(1995)

BO Gerber et al.

Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils

Curr Biol

(1997)

P Romagnani et al.

Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines

Am J Pathol

(1999)

A Moon et al.

Allergic gastroenteropathy in children

Ann Allergy Asthma Immunol

(1995)

AM Saavedra-Delgado et al.

Interactions between food antigens and the immune system in the pathogenesis of gastrointestinal diseases

Ann Allergy

(1985)

G Torpier et al.

Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein

Clin Exp Immunol

(1988)

SM Hill et al.

Colitis caused by food allergy in infants

Arch Dis Child

(1990)

GT Furuta

Eosinophils in the esophagus: acid is not the only cause

J Pediatr Gastroenterol Nutr

(1998)

RE Walsh et al.

The eosinophil in inflammatory bowel disease

Scand J Gastronenterol

(1991)

SK Sarin et al.

Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study

Dig Dis Sci

(1978)

AM Dvorak

Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: cytotoxic potential in Crohn's disease

J Immunol

(1980)

CA Liacouras et al.

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids

J Pediatr Gastroenterol Nutr

(1998)

LF Brown et al.

Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis

Am J Surg Pathol

(1984)

ME Rothenberg et al.

Gastrointestinal eosinophils

Immunol Rev

(2001)

H Nishitani et al.

Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis

J Gastroenterol

(1998)

S Khan et al.

Eosinophilic gastroenteritis: epidemiology, diagnosis and management

Paediatr Drugs

(2002)

JH Caldwell et al.

Serum IgE to eosinophilic gastroenteritis

N Engl J Med

(1975)

JP Cello

Eosinophilic gastroenteritis: a complex disease entity

Am J Med

(1979)

HH Scudamore et al.

Food allergy manifested by eosinophilia, elevated immunoglobulin E level, and protein-losing enteropathy: The syndrome of allergic gastroenteropathy

J Allergy Clin Immunol

(1982)

GT Furuta et al.

The role of the eosinophil in gastrointestinal diseases

Curr Opin Gastroenterol

(1995)

G Iacono et al.

Gastroesophageal reflux and cows milk allergy in infants: a prospective study

J Allergy Clin Immunol

(1996)

HA Sampson

Food Allergy

JAMA

(1997)

SV Walsh et al.

Allergic esophagitis in children: a clinicopathological entity

Am J Surg Pathol

(1999)

N Oyaizu et al.

Eosinophilic gastroenteritis: Immunohistochemical evidence for IgE mast cell-mediated allergy

Acta Pathol Jpn

(1985)

B Bates

‘Explosion’ of eosinophilic esophagitis in children

Pediatr News

(2000)

Cited by (751)

Colonic obstruction secondary to eosinophilic colitis in a neonate: A case report
2024, Journal of Pediatric Surgery Case Reports
Eosinophilic colitis (EC) is an uncommon inflammatory condition with the lowest reporting rate among eosinophilic gastrointestinal disorders. EC, which is characterized by the accumulation of eosinophilic cells, is typically diagnosed by a combination of clinical, imaging, and microscopic evaluations. We present a rare case of complete colonic obstruction due to eosinophilic colitis (EC) in a neonate, which was successfully managed with surgical intervention.
A 27-day-old female neonate presented with bloody diarrhea and anemia, followed by repeated bilious vomiting, feeding intolerance, and abdominal distention along with very limited bowel motion. Abdominal radiography showed contrast-medium retention in the colon with persistent bowel dilatation while a lower GI contrast enema indicated a cut-off sign at the level of the sigmoid colon. Subsequent colonoscopy revealed a rectosigmoid stricture with complete luminal obstruction 7 cm from the anal verge. Histopathological examination showed marked eosinophilic infiltration through all the layers of the colon. Exploratory laparotomy showed a 3-cm complete stricture with severe gross inflammation in the rectosigmoid colon. Resection of the affected segment and primary anastomosis was achieved successfully, and the patient showed an uneventful recovery with no symptoms at discharge as well as age-appropriate weight gain at the one-year follow-up examination.
To our knowledge, this is the first reported case of rectosigmoid stricture caused by EC in a neonate, and it highlights the importance of including EC in the differential diagnosis of colonic obstruction in neonates as well as the need for surgical management in such cases.
A case of eosinophilic gastroenteritis developed during administration of nivolumab for a patient with platinum-resistant head and neck cancer
2024, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
Eosinophilic gastroenteritis (EGE) is an inflammatory disease that causes symptoms related to dysfunction owing to the high infiltration of eosinophils into the gastrointestinal tissue. We report a case of EGE that developed after severe eosinophilia induced by nivolumab administration. A 53-year-old woman was diagnosed with recurrent neck lymph node metastasis of right tongue cancer and was referred to our hospital for chemotherapy. After the administration of 12 courses of nivolumab, grade 2 diarrhea was observed, and contrast-enhanced computed tomography (CT) revealed intestinal wall edema and stenosis of the small intestine. Symptoms improved with fasting, discontinuation of nivolumab, and administration of a proton pump inhibitor. Biopsy performed using a colon fiberscope revealed EGE. After resuming nivolumab and administering three courses, positron emission tomography/CT confirmed a complete response to the metastatic lesion, and nivolumab was discontinued. After discontinuation, mild eosinophilia persisted, but abdominal symptoms, such as diarrhea, did not recur. No signs of recurrence or metastasis were observed after two years.
Eosinophil Involvement Outside the Esophagus in Eosinophilic Esophagitis
2024, Clinical Gastroenterology and Hepatology
Allergenicity evaluation of fermented milk prepared by co-fermentation of Lactobacillus plantarum 7-2 and commercial starters after in vitro digestive
2023, Food Chemistry: X
Milk allergy is one of the most common food allergies, in which α_S-casein is the major milk allergen. Under optimized conditions, mixed starter (containing Lactobacillus plantarum 7-2 and commercial starter) effectively degraded α_S-casein of skimmed milk and reduced the pressure of stomach digestion. The fermented milk prepared by mixed starter was determined by ELISA, the antigenicity of α_S-casein was reduced by 77.53%. Compared with the fermented milk prepared by commercial starter, label-free quantitative proteomics demonstrated that the mixed starter more efficiently degraded the epitopes of major milk allergens and influenced the digestion pattern of the fermented milk. Therefore, L. plantarum 7-2 shows positive potential in reducing the antigenicity of α_S-casein and others. In addition, this study predicted that the new epitopes produced in the fermentation process could induce immunity using molecular simulation.
Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial
2023, The Lancet Gastroenterology and Hepatology
In eosinophilic gastrointestinal diseases, the role of eosinophils in disease pathogenesis and the effect of eosinophil depletion on patient outcomes are unclear. Benralizumab, an eosinophil-depleting monoclonal antibody that targets the interleukin-5 receptor α, might eliminate gastric tissue eosinophils and improve outcomes in eosinophilic gastritis. We aimed to assess the efficacy and safety of benralizumab in patients with eosinophilic gastritis.
We conducted a single-site, randomised, double-blind, placebo-controlled, phase 2 trial at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA). Individuals aged 12–60 years with symptomatic, histologically active eosinophilic gastritis (peak gastric eosinophil count ≥30 eosinophils per high-power field [eos/hpf] in at least five hpfs) and blood eosinophilia (>500 eosinophils per μL [eos/μL]) were randomly assigned (1:1, block size of four) to benralizumab 30 mg or placebo, stratified by the use of glucocorticoids for gastric disease. Investigators, study staff, and study participants were masked to treatment assignment; statisticians were unmasked when analysing data. Treatments were administered subcutaneously once every 4 weeks for a 12-week double-blind period (three total injections). The primary endpoint was the proportion of patients who achieved histological remission (peak gastric eosinophil count <30 eos/hpf) at week 12. Key secondary endpoints were the changes from baseline to week 12 in peak gastric eosinophil count, blood eosinophil count, eosinophilic gastritis histology (total, inflammatory, and structural feature scores), Eosinophilic Gastritis Endoscopic Reference System (EG-REFS) score, and patient-reported outcome symptom measures (Severity of Dyspepsia Assessment [SODA] and Patient-Reported Outcome Measurement Information System [PROMIS] short-form questionnaire). After the 12-week double-blind period, patients were eligible for entry into two open-label extension (OLE) periods up to week 88, in which all patients received benralizumab. Efficacy was analysed in the intention-to-treat (ITT) population and safety was assessed in all patients who received at least one dose of study drug. The trial was registered on ClinicalTrials.gov, NCT03473977, and is completed.
Between April 23, 2018, and Jan 13, 2020, 34 patients were screened, and 26 were subsequently randomly assigned to benralizumab (n=13) or placebo (n=13) and included in the ITT and safety populations (mean age 19·5 years [SD 7·3]; 19 [73%] male patients and seven [27%] female patients). At week 12, ten (77% [95% CI 50 to 92]) of 13 patients who received benralizumab and one (8% [1 to 33]) of 13 who received placebo achieved histological remission (difference 69 percentage points [95% CI 32 to 85]; p=0·0010). Changes from baseline to week 12 were significantly greater in the benralizumab group versus the placebo group for peak gastric eosinophil counts (mean –137 eos/hpf [95% CI –186 to –88] vs –38 eos/hpf [–94 to 18]; p=0·0080), eosinophilic gastritis histology total score (mean –0·31 [–0·42 to –0·20] vs –0·02 [–0·16 to 0·12]; p=0·0016), histology inflammatory score (mean –0·46 [–0·60 to –0·31] vs –0·04 [–0·22 to 0·13]; p=0·0006), and blood eosinophil counts (median –1060 eos/μL [IQR –1740 to –830] vs –160 eos/μL [–710 to 120]; p=0·0044). Changes were not significantly different between the groups for eosinophilic gastritis histology structural score (mean –0·07 [95% CI –0·19 to 0·05] vs 0·03 [–0·09 to 0·15]; p=0·23), EG-REFS score (mean –1·0 [–2·3 to 0·3] vs –0·5 [–2·0 to 1·0]; p=0·62), or in patient-reported outcomes (SODA and PROMIS). During the double-blind period, treatment-emergent adverse events occurred in 11 (85%) of 13 patients in the benralizumab group and six (46%) of 13 in the placebo group; the most common treatment-emergent adverse events were headache (six [46%] vs two [15%] patients), nausea (three [23%] vs two [15%]), and vomiting (two [15%] vs three [23%]). There were no treatment-related deaths. Two patients had serious adverse events (dizziness and rhabdomyolysis in one patient; aspiration in one patient) during the OLE periods, which were considered unrelated to study treatment.
Benralizumab treatment induced histological remission, as defined by absence of tissue eosinophilia, in most patients with eosinophilic gastritis. However, the persistence of histological, endoscopic, and other features of the disease suggest a co-existing, eosinophil-independent pathogenic mechanism and the need for broader targeting of type 2 immunity.
AstraZeneca and the Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).
Local type 2 immunity in eosinophilic gastritis
2023, Journal of Allergy and Clinical Immunology
Eosinophilic gastritis (EoG) associates with type 2 immunity. However, the type 2 cytokine cellular source, gastric T-cell composition, and gastric T-cell relationship (or relationships) with disease pathology remain understudied.
We defined gastric T-cell populations and their association with histologic and endoscopic EoG pathology.
Gastric biopsy samples (n = 6 EoG, n = 7 control) were subjected to histologic, endoscopic, and flow cytometry analyses. In a complementary cohort (n = 83 EoG), IL4, IL5, and IL13 mRNA levels were correlated with EoG pathologic parameters.
Gastric biopsy samples contained CD3⁺ T cells that were mainly CD8⁺; the CD8/CD4 ratio was comparable in EoG and control biopsy samples (5.7 ± 3.0 and 4.3 ± 0.6, respectively; P = .28). Gastric regulatory T (CD3⁺CD4⁺FOXP3⁺) and T_H2 (CD3⁺CD4⁺GATA3⁺) cell levels were increased in EoG versus controls (2-fold, P < .05 and 10-fold, P < .001, respectively) and correlated with gastric eosinophil levels (r = 0.63, P < .05 and r = 0.85, P < .001, respectively), endoscopic pathology (r = 0.56, P < .01; r = 0.84, P < .001, respectively), and histopathology (r = 0.72, P < .01; r = 0.82, P < .01, respectively). Cytokine-positive, most notably IL-4⁺, T_H2 cell levels strongly correlated with histologic and endoscopic scores (r = 0.82, P < .0001 and r = 0.78, P < .0001, respectively). In an independent EoG cohort (n = 83), bulk gastric IL4, IL5, and IL13 mRNA levels correlated with histologic score (r = 0.22, P < .005; r = 0.54, P < .0001; and r = 0.36, P < .0001, respectively) and endoscopic score (r = 0.27, P < .001; r = 0.40, P < .0001; and r = 0.35, P < .0001, respectively).
EoG is a T_H2 cell–associated disease featuring increased gastric type 2 cytokine–producing CD3⁺CD4⁺GATA3⁺T_H2 cells that strongly correlate with disease pathologies.

View all citing articles on Scopus

^☆

Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MD

This activity is available for CME credit. See page 41A for important information.

Supported in part by the Burroughs Wellcome Fund, the Human Frontier Science Program RG 264/99, the International Life Science Institute, National Institutes of Health/National Institutes of Allergy and Infectious Disease R01 AI42242 and AI45898, and the kind support of Martin Schlaff.

Disclosure of potential conflict of interest: M. E. Rothenberg has a consultant arrangement with Cambridge Antibody Technology and receives grants/ research support from Burroughs Wellcome.

View full text

Reviews and Feature ArticlesEosinophilic gastrointestinal disorders (EGID)☆

Abstract

Section snippets

Overview of eosinophilic gastrointestinal disorders

Eosinophil growth and development

Regulation of eosinophil tissue accumulation

Eotaxin subfamily of chemokines

Constitutive gastrointestinal eosinophils

Role of baseline eosinophils

Pro-inflammatory role of eosinophils in EGIDs

Clinical evaluation for EGIDs

Evaluation for HES in patients with apparent EGIDs

Eosinophilic esophagitis

Eosinophilic gastritis and gastroenteritis

Eosinophilic colitis

Summary and concluding remarks

Acknowledgments

Gastroenterology

J Pediatr

J Pediatr

Gastrointest Endosc

J Allergy Clin Immunol

Gastroenterology

Adv Immunol

Am J Gastroenterol

J Pediatr

J Allergy Clin Immunol

Gastroenterology

Baillieres Clin Gastroenterol

J Allergy Clin Immunol

Blood

J Allergy Clin Immunol

Crit Rev Oncol Hematol

J Allergy Clin Immunol

Semin Immunol

Adv Immunol

Gastroenterology

J Biol Chem

J Biol Chem

J Allergy Clin Immunol

J Biol Chem

Genomics

J Biol Chem

Curr Biol

Am J Pathol

Allergic gastroenteropathy in children

Ann Allergy Asthma Immunol

Interactions between food antigens and the immune system in the pathogenesis of gastrointestinal diseases

Ann Allergy

Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein

Clin Exp Immunol

Colitis caused by food allergy in infants

Arch Dis Child

Eosinophils in the esophagus: acid is not the only cause

J Pediatr Gastroenterol Nutr

The eosinophil in inflammatory bowel disease

Scand J Gastronenterol

Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study

Dig Dis Sci

Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: cytotoxic potential in Crohn's disease

J Immunol

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids

J Pediatr Gastroenterol Nutr

Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis

Am J Surg Pathol

Gastrointestinal eosinophils

Immunol Rev

Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis

J Gastroenterol

Eosinophilic gastroenteritis: epidemiology, diagnosis and management

Paediatr Drugs

Serum IgE to eosinophilic gastroenteritis

N Engl J Med

Eosinophilic gastroenteritis: a complex disease entity

Am J Med

Food allergy manifested by eosinophilia, elevated immunoglobulin E level, and protein-losing enteropathy: The syndrome of allergic gastroenteropathy

J Allergy Clin Immunol

The role of the eosinophil in gastrointestinal diseases

Curr Opin Gastroenterol

Gastroesophageal reflux and cows milk allergy in infants: a prospective study

Reviews and Feature Articles
Eosinophilic gastrointestinal disorders (EGID)☆