By: Jim LaValle, RPh,CCN, MT
A true IgE food allergy is 1 of the 4 symptom manifestations of the “atopic march,” along with
eczema, allergic rhinitis, and asthma.
It is clear if your pediatric patient has a true IgE food allergy because of the immediate IgE
immune response, making these classic type of food allergies easy to determine.
However, becoming more prevalent and harder to pinpoint,
are food intolerances and sensitivities. Specifically, identifying IgG, IgG4 and Complement
protein factors C3b and C3d delayed immune reactions are important to measure. The IgG
family of reactions can be difficult to recognize because of the vague and wide range of
symptoms which can take up to 72 hours to present.
Food sensitivities can develop over time, to some extent, because imbalances in the gut
microbiome or changes in gut permeability can take time to develop. The top
five food sensitivities in children are: gluten, dairy, corn, soy and eggs. The potential
consequences of consuming these foods, if the child has a sensitivity to one or more of them are,
chronic inflammation leading to skin disorders, GI problems such as eosinophilic esophagitis, as
well as asthma, autoimmunity and weight gain.
Potential signs of food intolerance in children:
- GI issues – stomach aches, constipation and/or diarrhea, burping/belching excessively, IBS,
IBDs - Frequent and prolonged crying
- Learning and behavioral problems
- Unexplained fatigue
- Immune/autoimmune issues
- Allergies/asthma
Copyright 2021 Jim LaValle
Potential signs of food intolerance in children (continued):
- Frequent infections, especially ear and throat
- Chronic low-grade fever
- Skin issues – irritations, rashes
- Unexplained weight gain or loss
- Sleep issues
- Neurological issues
- Autism Spectrum disorder
In early 1990s a study of 48 children between 6 months and 3 years of age
with food allergy/intolerance symptoms reported that 22.9% had specific IgE to food, 62.5% had
specific IgG and 14.6% had both specific IgE and IgG, while children without symptoms
of food allergy had neither specific IgE nor IgG to food. During the first three years of life, the
undesirable response to aliments is more often IgG-dependent than IgE-dependent. In fact, IgG
to milk, eggs and flour has been found two or three times more often than IgE.
Current literature supports the fact that pediatric food allergies, intolerances and sensitivities are
directly tied to pro-inflammatory sequelae and the release of GUT mucosal IgE and IgG type
antibodies. This inflammatory signaling “drives” metabolic, immunologic and
neurologic issues in pediatrics.
The GI tract is a significant source of chronic inflammatory signaling due to changes including
mucosal integrity and microbiome issues. Food allergies/sensitivities and intolerances can play a
significant role in gut permeability and related gut health
An altered microbiome, directly reflecting changes in microbiota, is not only a marker of
disease but also actively contributes to metabolic and neurologic issues in pediatrics.
Importance of Pediatric GUT Health
Emerging research of the pediatric microbiome demonstrates its importance in the development
of GUT mucosal integrity, the immune system, nervous system, and growth in children.
Undesirable dysbiotic changes to the microbiome during infancy are directly related to the
development of chronic illnesses such as asthma, allergies, and inflammatory bowel disease.
Dysbiosis is associated with many other conditions such as ADHD, autism, obesity and type 2
diabetes in children. Conversely a healthy pediatric microbiome provides protection against
various pathogens, adverse vaccine responses and drug metabolism.
Statistics for GUT-Immune Allergic and Related Conditions in Pediatrics:
- Functional gastrointestinal disorders are one of the most common complaints in children and
adolescents including functional abdominal pain. Worldwide prevalence of function abdominal
pain is 13.5% of the pediatric population, of which irritable bowel syndrome was the most
prevalent (8.8%). - Ear infections are the most common reason parents bring their child to a doctor. Three out of
four children will have at least one ear infection by their third birthday. - Asthma is the most common chronic condition among children, currently affecting an
estimated 6.1 million children in the US under 18 years, of which 3.5 million suffered from an
asthma attack or episode in 2016. - CDC estimates that since 2010, flu-related hospitalizations among children younger than 5
years old have ranged from 7,000 to 26,000 in the United States; children younger than 5 years
old – especially those younger than 2 – are at high risk of developing serious flu-related
complications. - 23.6% of children aged 0-18 years’ experience a skin allergy.
- 20.3% of children aged 6-11 years are obese.
Unfortunately, the rate of childhood obesity has increased in parallel with adult obesity, resulting
in pediatric patients presenting with diseases traditionally associated with adulthood such as
dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Food intolerance
reflected by immunoglobulin G (IgG) antibodies may predispose the child to low grade
inflammation and atherogenesis. A 2007 study using obese juveniles reported a highly
significant increase in intima media thickness (IMT), elevated CRP values and anti-food IgG
antibody concentrations compared to normal weight juveniles. Anti-food IgG showed tight
correlations with CRP and IMT and sustained highly significant in a multiple regression model.
Factors including vaginal delivery, breastfeeding, maternal health and nutrition help shape the
microbiome. Caesarian delivery, formula feeding, poor dietary choices and antibiotic use can
alter microbiome diversity and are associated with the development of chronic health issues like
GI disorders, diabetes, asthma, allergic diseases, autoimmunity and obesity later in life.
Autism and Food Intolerances/Sensitivities
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition described by
impairments in three main behavioral areas: social deficits, impaired communication, and
repetitive behaviors. Despite many years of vast study, the causes of ASD are still unknown.
Various risk factors including genetic, infectious, metabolic and immunological have been
suggested along with environmental, nutritional and metabolic related risk factors.1
Children with ASD often show intolerance to one or more foods. Food proteins and protein-
derived compounds may modulate the immune response in the body. Changes in gut
permeability may lead to food-borne immune complexes and pathogens being allowed into blood
circulation. This results in an abnormal immune response and increased levels of circulating pro-
inflammatory cytokines. Studies report that gluten and casein intolerance in children with ASD
often have high-level specific IgG antibodies. These GUT-IMMUNE abnormalities may
explain, in part, the pathogenesis of ASD.
Studies using IgE antibody tests report that autistic children routinely have higher levels of IgE
antibodies. A 2020 study investigated aberrant eating behaviors (EBs), gastrointestinal (GI)
symptoms, and food intolerance in children with autism spectrum disorder (ASD) and their
association with clinical core symptoms of ASD in 94 preschool children diagnosed with ASD.
For placebo, 90 children with typical development (TD) were also used. Questionnaires were
used along with serum specific IgG antibodies against 14 kinds of food were detected using
enzyme-linked immunosorbent assays (ELISAs). Results were that the detection rate of aberrant
EBs in the ASD group was significantly higher than that in the TD group (67.39 vs. 34.94%),
and the rate of GI symptoms was also higher in the ASD group than that in the TD group (80.22
vs. 42.11%). Detection of food intolerance in children with ASD reported a positive rate of
89.89% and that the majority of children had multiple food intolerances. The authors concluded
that ASD with aberrant EBs or high food-specific IgG antibodies concentrations had more severe
stereotyped behavior, which may have implications for exploring the immune mechanism of
ASD.
Conclusion
Testing for IgE, IgG, IgG4 and Complement factor proteins C3b and C3d is an important tool for
pediatricians to utilize in children with GUT, immune, metabolic and other chronic health issues.
Certain foods may trigger GUT microbiome issues that then disrupt GUT-Brain and GUT-
Immune signaling, thereby leading to increased symptoms in the child.
Prescribing a diet that eliminates the foods that cause these responses decrease many types of
inflammation. This allows for a down regulation of symptoms and may promote gut healing and
is foundational to the well-being of the child.
References
[1] Hofman T. IgE and IgG antibodies in children with food allergy. Rocz Akad Med Bialymst.
1995;40(3):468-73.
[1] Ohtsuka Y. Food intolerance and mucosal inflammation. Pediatr Int. 2015;57(1):22-9.
[1] Chahine BG, et al. The role of the GUT mucosal immunity in the development of tolerance
versus development of allergy to food. Curr Opin Allergy Clin Immunol. 2010;10(4):394-9.
[1] Berlin MC. Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin
Immunopathol. 2012;34(5):633-42.
[1] Lobionda S, et al. The role of gut microbiota in intestinal inflammation with respect to diet
and extrinsic stressors. Microorganisms. 2019;7(8):271.
[1] Ihekweazu FD, et al. Development of the pediatric gut microbiome: impact on health and
disease. Am J Med Sci. 2018;356(5):413-23.
[1] Korterink JJ, et al. Epidemiology of pediatric functional abdominal pain disorder: a meta-
analysis. PLoS One. 2015;10(5):e0126982.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-
lookup/asthma/learn-about-asthma/asthma-children-facts-sheet Accessed February 2021.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] Wilders-Truschnig M, et al. IgG antibodies against food antigens are correlated with
inflammation and intima media thickness in obese juveniles. Exp Clin Endocrinol Diabetes.
2008;116(4):241-5.
[1] Karakula-Juchnowicz H, Gałecka M, Rog J, Bartnicka A, Łukaszewicz Z, Krukow P, et al.
The food-specific serum IgG reactivity in major depressive disorder patients, irritable bowel
syndrome patients and healthy controls. Nutrients. 2018;10:548.
[1] Bavykina I, Popov V, Zvyagin A, Bavykin D. Frequency of determining markers of casein’s
inhability and gluten in children with disorders of autistic spectrum. Vopr Pitan. 2019;88:41–7.
[1] Hofman T. IgE and IgG antibodies in children with food allergy. Rocz Akad Med Bialymst.
1995;40(3):468-73.
[1] Ohtsuka Y. Food intolerance and mucosal inflammation. Pediatr Int. 2015;57(1):22-9.
[1] Chahine BG, et al. The role of the GUT mucosal immunity in the development of tolerance
versus development of allergy to food. Curr Opin Allergy Clin Immunol. 2010;10(4):394-9.
[1] Berlin MC. Mucosal antibodies in the regulation of tolerance and allergy to foods. Semin
Immunopathol. 2012;34(5):633-42.
[1] Lobionda S, et al. The role of gut microbiota in intestinal inflammation with respect to diet
and extrinsic stressors. Microorganisms. 2019;7(8):271.
[1] Ihekweazu FD, et al. Development of the pediatric gut microbiome: impact on health and
disease. Am J Med Sci. 2018;356(5):413-23.
[1] Korterink JJ, et al. Epidemiology of pediatric functional abdominal pain disorder: a meta-
analysis. PLoS One. 2015;10(5):e0126982.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-
lookup/asthma/learn-about-asthma/asthma-children-facts-sheet Accessed February 2021.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] Centers for Disease Control (CDC). www.cdc.gov. Accessed February 2021.
[1] Wilders-Truschnig M, et al. IgG antibodies against food antigens are correlated with
inflammation and intima media thickness in obese juveniles. Exp Clin Endocrinol Diabetes.
2008;116(4):241-5.
[1] Karakula-Juchnowicz H, Gałecka M, Rog J, Bartnicka A, Łukaszewicz Z, Krukow P, et al.
The food-specific serum IgG reactivity in major depressive disorder patients, irritable bowel
syndrome patients and healthy controls. Nutrients. 2018;10:548.
[1] Bavykina I, Popov V, Zvyagin A, Bavykin D. Frequency of determining markers of casein’s
inhability and gluten in children with disorders of autistic spectrum. Vopr Pitan. 2019;88:41–7.
