Journal of Food Allergy

145 Pages·2012·3.33 MB·English

JOURNAL OF
FOOD ALLERGY
Official Journal of the Brazilian Society of Food Allergy
Printed Version ISSN 2238-0752 January-March 2012 • Volume 1 • Number 1
J FOOD ALLERGY
JOURNAL OF FOOD ALLERGY
EDITORIAL BOARD
Offi cial Journal of the Brazilian Society of Food Allergy - SBAA
EDITOR-IN-CHIEF
Prof. Aderbal Sabra
University Unigranrio, Rio de Janeiro, Brazil
CONSULTING EDITORS
Katie Allen John Walker-Smith
University of Melbourne, Melbourne, Australia Emeritus Prof of Paediatric Gastroenterology
University of London, Londo, United Kingdom
Jaime Ramirez Mayans
Marcello Barcinski
Instituto Nacional de Pediatría, S.S, Mexico
FIOCRUZ, Rio de Janeiro, Brazil
Joseph A. Bellanti
Georgetown University Medical Center, USA Mauro Batista Morais
Paulista School of Medicine, Sao Paulo, Brazil
Jorge Amil Dias
Centro Hospitalar S. Joao, Portugal Simon Murch
Warwick Medical School, United Kingdom
Jorge Kalil
School of Medicine USP and
Annamaria Staiano
Instituto Butantan, São Paulo, Brazil
University of Naples, Federico II, Italy
Giuseppe Iacono
Maria Del Carmen Toca
Di Cristina Hospital, Italy
University of Buenos Aires, Argentina
Glenn Furuta
Neil Shah
Univ. of Colorado Denver School of Medicine, USA
Great Ormond Street Hospital
Olivier Goulet Institue of Child Health
University of Paris 5 René Descartes, Paris, France University College London, United Kingdom
Harland Winter
Harvard Medical School, USA
Journal of Food Allergy
Address: Visconde de Piraja, 330 / 311, 22410-001, Rio de Janeiro, Brazil
Telephone: + 55 21 2513-2161
E-mail: [email protected]
Website: www.journalfoodallergy.com
J FOOD ALLERGY
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JOURNAL OF FOOD ALLERGY
Volume 1, Number 1 January - March, 2012
CONTENTS
Editor’s Comment
Aderbal Sabra.............................................................................................................................................................. 03
Original Articles
Atopy in children with Eosinophilic Esophagitis (EoE) and Gastroesophageal Refl ux Disease (GERD)
Heather Cassell, Vincent Mukkada, Samantha A. Woodruff, Stephanie Petersburg, Zhaoxing Pan,
Dan Atkins, Glenn T. Furuta, David Fleischer ........................................................................................................... 05
Gastrointestinal and Behavioral Dysfunction in Children with Non-IgE-mediated Food Allergy, Ileal-Nodular-
Lymphoid Hyperplasia (ILNH) and Low Th1 Function: A New Clinical-Immunologic Constellation
Aderbal Sabra, Joseph A. Bellanti, Dan Hartmann, Barbara Zeligs, Selma Sabra, Ricardo Ebecken,
Kalil Madi, Isaac Tenório .......................................................................................................................................... 12
Are mothers of infants aware of the peanut and egg allergen content of foods?
Jennifer Koplin, Shyamali C. Dharmage, Lyle C. Gurrin, Nicholas J. Osborne, Mimi L. K. Tang,
Katrina J. Allen ........................................................................................................................................................... 20
Cytokines Profi les in Patients with the Spectrum of Non-IgE Food Allergy: A New Prototype of Immunological
Disturbance
Aderbal Sabra, Joseph Alphonso Bellanti, Selma Sabra, Barbara Zeligs, Gustavo Rodrigues,
Isaac Tenório .............................................................................................................................................................. 28
Review Article
Eosinophilic esophagitis in children: Basic concepts
Ruben Rocha, Jorge Amil Dias ................................................................................................................................... 35
Information for Authors ........................................................................................................................................... 44
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EDITOR’S COMMENT
Finally the world literature has a journal of medicine totally devoted to the study of food allergy and related
sciences.
Our refi ned Editorial Board with members from all over the world, all of then with a large experience in
different fi elds of food allergy is signaling that JFA has come to take place and emerge as a unique journal deeply
enrolled and compromised with all the sciences related to food allergy.
From the bench housing the basic science to the clinical affairs JFA has compromised itself to publish
papers that could cover all the fi elds of food allergy. For this reason our editorial board has a unique fashion with
members dedicated to basic sciences, to others dedicated to different fi elds of the clinical aspects of food allergy.
This selected group of editors will take care, as leaders in their fi elds, of the excellence and quality of our selected
papers to be published in JFA.
Is our goal to run for indexation, so we will start with the minimum of four issues per volume-year with all
papers in accordance with the rules originated by the house of experts in NIH.
Our fi rst issue, volume one number one, will appear “on line” soon, with an innovation of free access to all
readers, in tree idioms: English, Portuguese and Spanish. An English edition is “in press” and will be published to
be distributed to selected libraries, all over the world. Editions “on line” in Japanese, Russian and Chinese are on
the way.
Issue number one has fi ve articles:
1 - Atopy in children with Eosinophilic Esophagitis (EoE) and Gastroesophageal Refl ux Disease (GERD) -
Heather Cassell, Vincent Mukkada, Samantha A. Woodruff, Stephanie Petersburg, Zhaoxing Pan, Dan Atkins,
Glenn T. Furuta, David Fleischer Alvernon Allergy Asthma and Asthma P.C, Tucson, Arizona, (HC); Hasbro Chil-
dren’s Hospital, Alpert Medical School, Brown University, Providence, RI, (VM); Department of Pediatrics, Uni-
versity of Massachusetts, Worcester, MA, (SAW); Digestive Health Institute, Section of Pediatric Gastroenterology,
Hepatology, and Nutrition, Children’s Hospital Colorado, Aurora, Colorado, (SP, GTF); Department of Pediatrics,
University of Colorado Denver School of Medicine (ZP, DA, GTF, DF); Department of Pediatrics, National Jewish
Health, Denver, Colorado, USA (DA, GTF, DF);
2 - Gastrointestinal and Behavioral Dysfunction in Children with Non-IgE-mediated Food Allergy, Ileal-Nod-
ular-Lymphoid Hyperplasia (ILNH) and Low Th1 Function: A New Clinical-Immunologic Constellation - Ad-
erbal Sabra, Joseph A. Bellanti, Dan Hartmann, Barbara Zeligs, Selma Sabra, Ricardo Ebecken, Kalil Madi, Isaac
Tenorio, Department of Food Allergy UNIGRANRIO, Rio de Janeiro, Brazil (AS, IT) and ICIS Immunology
Service at Georgetown University, USA (AS); Department of Microbiology and Immunology and Director of ICIS
at Georgetown University, USA, (JAB); Pathology Service at Georgetown University, USA, (DH); Laboratory of
Immunology at Georgetown University, USA, (BZ); Pediatric Endoscopy Service HUAP-UFF, Rio de Janeiro,
Brazil (SS, RE); Department of Pathology UNIGRANRIO, Rio de Janeiro, Brazil, (KM);
3 - Are mothers of infants aware of the peanut and egg allergen content of foods? - Jennifer Koplin, Shyamali
C. Dharmage, Lyle C. Gurrin, Nicholas J. Osborne, Mimi L. K. Tang, Katrina J. Allen Murdoch Childrens Re-
search Institute (JK, SCD, LCG, NJO, MLKT, KJA), Department of Paediatrics (JK, MKT, KJA), University of
Melbourne; Department of Allergy and Immunology (MLKT, KJA), Royal Children’s Hospital The Centre for
Molecular, Environmental, Genetic and Analytic Epidemiology (SCD, LCG), University of Melbourne, Parkville,
VIC, Australia and European Centre for Environment and Human Health (MJO), Peninsula College of Medicine
and Dentistry, University of Exeter, United Kingdom;
3
J FOOD ALLERGY
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EDITOR’S COMMENT -
Continued
4 - Cytokines Profi les in Patients with the Spectrum of Non-IgE Food Allergy: A New Prototype of Immunologi-
cal Disturbance - Aderbal Sabra, Joseph Alphonso Bellanti, Selma Sabra, Barbara Zeligs, Gustavo Rodrigues, Isaac
Tenório, Department of Gastroenterology and Food Allergy, UNIGRANRIO University - School of Medicine, RJ,
Brazil, (AS); Department of Immunology Center – ICISI – Georgetown University, Washington, DC, USA, (JAB);
Department of Pediatrics, UNIGRANRIO University, RJ, Brazil, (SS); Department Pediatric Endoscopy, Antônio
Pedro University Hospital, RJ, Brazil, (BZ); Laboratory of Immunology, Immunologic Center – ICISI – George-
town University, Washington, DC, USA, (GR); Department of Pediatric Gastroenterology and Food Allergy, UNI-
GRANRIO University, RJ, Brazil, (IT);
5 - Eosinophilic esophagitis in children: Basic concepts - Ruben Rocha, Jorge Amil Dias - Department of Pediat-
rics, Centro Hospitalar S. João, Porto, Portugal.
We are running issue number two and “call for papers” are under way to the next issues. Please send your
manuscripts to JFA (www.journalfoodallergy.com), from basic science to clinical experience. All articles are wel-
come, “bem vindos” and “bien venidos”. Our editorial board will appreciate to select then to be published in JFA.
Welcome to our fi rst issue.
Aderbal Sabra, MD, PhD
Editor-in-Chief
Journal of Food Allergy
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ORIGINAL ARTICLE
Journal of Food Allergy, Vol. 01 (1): 05-11, January-March - 2012
Atopy in children with Eosinophilic Esophagitis (EoE) and
Gastroesophageal Refl ux Disease (GERD)
Heather Cassell, Vincent Mukkada, Samantha A. Woodruff, Stephanie Petersburg, Zhaoxing
Pan, Dan Atkins, Glenn T. Furuta, David Fleischer
Alvernon Allergy Asthma and Asthma P.C., Tucson, Arizona, (HC); Center for Children’s Digestive Diseases,
Hasbro Children’s Hospital, Alpert Medical School, Brown University, Providence, RI, (VM); Department of
Pediatrics, University of Massachusetts, Worcester, MA, (SAW); Digestive Health Institute, Section of Pediatric
Gastroenterology, Hepatology, and Nutrition, Children’s Hospital Colorado, Aurora, Colorado, (SP, GTF); Gas-
trointestinal Eosinophilic Diseases Program, Department of Pediatrics, University of Colorado Denver School of
Medicine (ZP, DA, GTF, DF); Department of Pediatrics, National Jewish Health, Denver, Colorado, USA (DA,
GTF, DF)
ABSTRACT
Background: Eosinophilic esophagitis (EoE) is often confused with gastroesophageal refl ux disease (GERD). Identifi ca-
tion of clinical clues that could assist in differentiating EoE from GERD would be benefi cial. Co-morbid allergic diseases
occur commonly in adults and children with EoE. To date, few studies have compared the incidence of allergic diseases
in children with EoE to those with GERD.
Objectives: To determine the incidence of allergic diseases in children with EoE and GERD.
Materials and Methods: A retrospective chart review was performed of patients who were evaluated in a multidisciplinary
program caring for children with eosinophilic gastrointestinal diseases. Data regarding the presence of allergic disease
(IgE-mediated food allergy, asthma, allergic rhinitis, and eczema, as well as relevant skin and serum food-specifi c-IgE
testing and total serum IgE) were recorded.
Results: Charts from 116 patients (ages 1-18 years) were reviewed. Patients with EoE had a signifi cantly higher per-
centage of atopic diseases (IgE-mediated food allergy, asthma, allergic rhinitis, and/or eczema) compared to those with
GERD (89.1% versus 50%, p=0.001). Patients with EoE had a higher percentage of allergic rhinitis (62.5% vs 35%,
p=0.03), eczema (56.3% vs 30%, p=0.04), and environmental allergen sensitivity (87% vs 46%, p=0.001) (based on
positive allergy tests), as well as peripheral blood eosinophilia (51% vs 11%, p=0.005) compared to those with GERD.
Conclusions: A history of allergic diseases in children with common gastrointestinal symptoms aids in identifying those
more likely to have EoE.
Key words: Eosinophilic Esophagitis; Gastroesophageal Refl ux
J Food Allergy. 2012; 1: (1) 05-11
INTRODUCTION
relaxations of the lower esophageal sphincter, EoE is
attributed to chronic allergic infl ammation. Although
Common gastrointestinal symptoms
GERD and EoE are pathophysiologically distinct,
such as vomiting, feeding intolerance, abdominal
the commonality of their presenting symptoms often
pain and dysphagia are the initial symptoms of
results in children being misdiagnosed with GERD
gastroesophageal refl ux disease (GERD) and
when they actually have EoE. Clinical experiences
eosinophilic esophagitis (EoE) (1). While the
also have identifi ed a group of patients with EoE
pathophysiology of GERD is related to transient
who have co-existent GERD; the pathophysiology
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Atopy in children with Eosinophilic Esophagitis
of this subgroup of patients is still not known (2,3). Some patients had a clinico-pathological response
Therefore, an understanding of how often to topical steroids or dietary exclusions but then
allergic symptoms occur in children with EoE developed heartburn or abdominal pain that was
compared to those with the more prevalent GERD responsive to proton pump inhibition. These
would be benefi cial. An increasing number of patients were considered to have EoE + GERD.
studies and clinical experiences have identifi ed the The presence of a systemic food reaction
association of EoE with other co-morbid allergies (generalized urticaria and/or more than one organ
such as IgE-mediated food allergy, asthma and system involved in a reaction occurring <2 hours after
eczema. To date, few studies have compared the food ingestion), asthma, allergic rhinitis and eczema
incidence of atopic diseases in children with EoE was determined by the allergist. Environmental
compared to those with the more common GERD allergen sensitivity was defi ned by having either
(4-8). a positive skin prick test or an elevated specifi c
We hypothesize that children with EoE have IgE to an environmental allergen; eosinophilia
an increased incidence of allergic diseases compared was defi ned as a total peripheral eosinophil count
to those with GERD. The objective of this study greater than 500/μL and an elevated IgE was
was to measure the presence of allergic disease in determined based on age-related normal values.
a cohort of children evaluated in a multidisciplinary This study was performed with the approval
eosinophilic gastrointestinal diseases program. of the Colorado Multi-Institutional Review Board and
the National Jewish Health Institutional Review Board.
MATERIAL AND METHODS
Data Analysis
Patient Selection Chi-square and Fisher’s exact test were
A retrospective chart review was performed used to analyze the differences in comorbid
of all patients evaluated in the Gastrointestinal diseases and allergy testing between patients with
Eosinophilic Diseases Program at Denver, Colorado EoE, EoE + GERD, GERD or other diagnoses.
from December 2007 to March 2009. A pediatric
gastroenterologist and pediatric allergist evaluated RESULTS
all patients. Charts were reviewed to identify the
presence or absence of key clinical features of allergic The charts from 183 patients were available
diseases and the results of specifi c allergy testing (skin for review. Sixty-seven patients records were not
prick testing, total IgE, allergen-specifi c IgE levels).
included as their evaluations were not yet complete or
A diagnosis of EoE was made in children
they were older than18 years of age. Of the 116 patients
who presented with a chronic history of abdominal
used for analysis, 57.2 to 55.2% had EoE, 8.6% had
pain, dysphagia, food impaction, anorexia or failure
both EoE and GERD, 17.2% had GERD alone and
to thrive, an esophageal biopsy with greater than
18.9 to 19% had alternative diagnoses. Alternative
15 eosinophils per HPF and normal gastric and
diagnoses included eosinophilic colitis, infl ammatory
duodenal biopsies. Other causes for these fi ndings
bowel disease, constipation, food protein-induced
were eliminated (1). As a part of this evaluation, a
enterocolitis syndrome, celiac disease, Chiari
number of children were found to have alternative
causes of their symptoms and histopathological malformation, intestinal lymphangiectasia, gastritis
fi ndings. In this regard, diagnostic criteria for and irritable bowel syndrome. Patient demographics
GERD included a clinical or pathologic response showed a higher percentage of male patients for
to a proton pump inhibitor (PPI) and/or a positive EoE, EoE + GERD, and GERD populations, but not
impedance or esophageal pH monitoring study. for other diagnoses (Table 1).
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Atopy in children with Eosinophilic Esophagitis
Table 1. Patient demographics.
Diagnosis Number of Patients Median Age Percent Male
(range)
EoE 64 9.5 yrs.(2-18) 70%
EoE + GERD 10 8.3 yrs.(2-16) 90%
GERD 20 7.5 yrs.(2-16) 95%
Other 22 5.2 yrs.(2-13) 50%
Children with EoE had a signifi cantly higher DISCUSSION
percentage of any atopic disease (IgE-mediated food
allergy, asthma, allergic rhinitis, and/or eczema) As the worldwide incidence of EoE has
compared to those with GERD (89.1% vs 50%, increased, so has the clinical confusion differentiating
p=0.001; Table 2 and Figure 1). Children with EoE EoE from GERD. This confusion is emphasized
had a signifi cantly higher percentage of allergic by the fact that over 33% of patients referred to
rhinitis (62.5% vs 35%, p=0.03), and a higher rate our multi-disciplinary program, which focuses on
of eczema (56.3% vs 30%, p=0.04) than those with eosinophilic gastrointestinal diseases (EGIDs),
GERD alone. Children with EoE + GERD also had actually had a diagnosis other than an EGID. To
signifi cantly higher percentages of asthma, allergic begin to address this, we examined whether allergic
rhinitis, or eczema than children with GERD alone diseases and abnormal lab values / positive skin
(p=0.01; Table 2 and Figure 1). Finally, there was prick tests occurred with different incidences in
a higher percentage of environmental allergen children with EoE and GERD. Measurements
sensitivity (87% vs 46%, p=0.001) and peripheral of these parameters were important to provide
blood eosinophilia (51% vs 11%, p=0.005; Figure additional clinical features that may help distinguish
2) in children with EoE compared to those with between these two diseases. Results here document
GERD. There were no signifi cant differences that the incidence of allergic diatheses, specifi cally
in total IgE levels identifi ed among the groups. IgE-mediated food allergy, asthma, allergic rhinitis
Table 2. Comparison of prevalence of allergic features in children with intestinal diseases.
Diagnoses Systemic Asthma Allergic Eczema Any Environmental Eosinophilia Elevated
Compared Food (p Rhinitis (p Atopic Allergen (p value) IgE
Reaction value) (p value) Feature Sensitivity (p value)
(p value) value) (p value) (p value)
EoE vs. 0.167 0.225 0.031* 0.040* 0.001*** 0.002** 0.005** 0.546
GERD
EoE vs. 0.181 0.782 0.451 0.824 0.272 0.966 0.637 0.822
EoE+GERD
EoE vs. 0.015* 0.137 0.013* 0.214 0.002** 0.014* 0.004** 0.414
Other
EoE+GERD 0.760 0.284 0.429 0.114 0.006** 0.058 0.150 0.571
vs. GERD
EoE+GERD 0.646 0.210 0.325 0.316 0.017* 0.127 0.084 0.778
vs. Other
GERD vs. 0.349 0.845 0.827 0.461 0.554 0.682 0.665 0.255
Other
*p<0.05, **p<.01, ***p<.001
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Atopy in children with Eosinophilic Esophagitis
Figure 1. Incidence of allergic diseases.
Figure 2. Analysis for allergic diseases.
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Atopy in children with Eosinophilic Esophagitis
and eczema, was signifi cantly greater in children in children with EoE. This is important for several
with EoE compared to those with GERD. Although reasons. First, these fi ndings provide additional
peripheral eosinophilia was more common in children clinical data to support a diagnosis of EoE when
with EoE, we were interested to fi nd that the frequency evaluating children with common gastrointestinal
of an elevated IgE levels, a laboratory value typically
complaints. Second, IgE has been proposed as a key
associated with EoE, was not signifi cantly different
molecule in the pathogenesis of EoE. In this study,
between the two groups. Our results also indicate
elevated total IgE levels did not differ signifi cantly
that 50% of the pediatric GERD population had
between children with EoE and those with GERD,
a history of an allergic disease, a value somewhat
whereas the presence of allergen-specifi c IgE as
higher than suspected. Taken together, these fi ndings
determined by serum allergen-specifi c IgE levels
show that atopic disorders occur more frequently in
and skin prick testing was different between groups.
children with EoE compared to those with GERD.
This suggests that total IgE levels alone may not be
This may be helpful in differentiating these two
a valuable measure of allergy in patients with EoE
disorders, as these diagnoses are often confused.
and reliance on allergen specifi c IgE levels may
While the overall incidence of allergic
be more appropriate to assess suspected patients.
diseases, such as asthma and food allergy, is clearly
Third, we show that the patients with EoE +
increasing, the identifi cation of specifi c subsets of
GERD have a profi le of allergic disease that is very
children who develop these diseases has not been
similar to the EoE group. This fi nding suggests that
studied extensively. Pomiecinski et al evaluated 69
children can have both EoE and GERD, and in this
adults with a history of heartburn and found that
situation, EoE may be the predominant condition.
27% had sensitization to foods as determined by
A variety of other measures may help to
skin prick testing (8). Garcia-Compean determined
distinguish EoE from GERD including the number
that atopy occurred more frequently in adults with
of esophageal eosinophils per high powered
symptoms refractory to PPI treatment (7). Dalby et
fi eld (9), eosinophil degranulation (10), tryptase
al. found that food sensitization, based on skin prick
staining for mast cell identifi cation (11), esophageal
testing, atopy patch testing and elevated allergen
fi brosis index (12,13), cytokine analysis (14)
specifi c IgE levels occurred more frequently in
and endoscopic features (15). To date, only pH
children with EoE than those with GERD (6).
monitoring and / or a clinico-pathological response
Gupta et al. compared a variety of allergic features
to PPI treatment are suffi cient to differentiate EoE
(allergic rhinitis, asthma, eczema, total IgE levels,
from GERD (1). In isolation, no other clinical
peripheral eosinophilia, serum allergen-specifi c IgE,
features, including the eosinophil enumeration
and skin prick testing) from 68 children with EoE to
or the presence of allergic features as shown
23 with GERD, and discovered that only peripheral
here, can provide this level of diagnostic clarity.
eosinophilia was signifi cantly greater in the EoE
Several issues should be considered
group (5). Finally, Aceves et al. found that children
when interpreting our fi ndings. Records reviewed
with EoE had signifi cantly more asthma and food
were from children cared for in a tertiary care
allergy, but not allergic rhinitis, compared to children
multidisciplinary allergy/GI program who were
with GERD (4). Thus, while the preponderance
already suspected of having an allergic disease,
of data suggests that patients with EoE have
EoE. Thus, it is not surprising that the comparison
more allergic diatheses, not all parameters are
groups (GERD and others) have a high level of
increased when comparing to children with GERD.
allergic diseases. Since children in this study
Our fi ndings do reinforce the clinical
were taken from this highly selected group, we
suspicion that allergic diseases occur more frequently
anticipate that children with GERD taken from a
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