I recently read this article: A Case of Severe Atypical Food Protein Induced Enterocolitis Syndrome (abstract here).
It is a short article published in Allergy journal in August 2010 about a case of a severe reaction to cow's milk in a 4yr.old boy. "The article highlights the potential severity of this condition and its capacity to present beyond infancy".
This 4yr.old boy, with a history of developmental delays had been receiving his extensively hydrolyzed cows milk formula via tube feedings since infancy. He had ongoing eczema and a history of GERD; but otherwise had no other indications of allergy past infancy. He was given unhydrolyzed cows milk formula in an overnight feed, within 2hours he was showing discomfort and began to have frequent watery stools (every 10-15min), which progressed to bloody stools within 2hrs.,so the feedings were stopped, and he was also having significant shortness of breath so was taken to the ER.
The article goes on to describe how he presented in the ER without fever (actually had low body temp), had low blood pressure and also acidotic and significant shortness of breath. Further labs also revealed increased methaemoglobin, neutrophils and platelet levels. He was treated for his symptoms of presumed septicemia and remained in the hospital; although extensive work up could not find a source for his symptoms. Follow up endoscopy was performed 3 weeks following this episode and biopsy findings revealed gastritis and eosinophlic infiltrate in the colon. He was resumed on his tube feedings with an elemental formula.
The conclusion of the article highlights that FPIES is a "complex of vomiting, diarrhea, and systemic inflammatory response because of Non-IgE food allergy". The authors note that this case is outside of the published criteria for typical FPIES but that it illustrates the severity of this type of allergy and that it is possible to have an FPIES response beyond infancy. The authors conclude the article with a very important message about FPIES, "FPIES is frequently misdiagnosed, and children often have several acute presentations before the diagnosis is established. In view of its potentially fatal clinical course and the recent increase in prevalence suggested by others, it is critical to consider the diagnosis in young children presenting with acute onset of gastrointestinal symptoms or shock".
Showing posts with label Non-IgE Allergy. Show all posts
Showing posts with label Non-IgE Allergy. Show all posts
Thursday, November 3, 2011
Saturday, July 9, 2011
"In truth, question everything"....
This blog post on an allergy blog I follow: Grading the Severity of your Allergy: Sensitivity vs. Reaction Level, gives good advice on how to decipher your reaction levels, your severity. What do you (or your child) react to? Everything in the air? Cross contamination? Trace proteins? Food families? Through breastmilk? Through feed from the animal contaminating the meat? Through formula? On the skin?
With Non-IgE allergy, just as with an IgE Allergy, even the blood and skin tests will not tell the severity of an allergy; it will only tell the positive antibody production and the probability of reaction. The only tried and true way to tell a person's reaction level is by testing it with elimination and challenge. Eliminate the food from the diet, if symptoms subside, there are good chances you are allergic and need to eliminate that food, and all derivatives of it from the diet. Some reaction symptoms are obvious enough you don't have to, nor would you want to, challenge the food. A challenge would consist of a re-introduction of the food once suspected symptoms have resolved. This challenge can also help determine severity of the allergy; as addressed in the above blog article. Some people react to any and all minute derivatives or cross contamination of the allergen, some can handle derivatives or oils, etc. The only true way to know is to challenge, and in the meantime- question everything.
With Non-IgE allergy, just as with an IgE Allergy, even the blood and skin tests will not tell the severity of an allergy; it will only tell the positive antibody production and the probability of reaction. The only tried and true way to tell a person's reaction level is by testing it with elimination and challenge. Eliminate the food from the diet, if symptoms subside, there are good chances you are allergic and need to eliminate that food, and all derivatives of it from the diet. Some reaction symptoms are obvious enough you don't have to, nor would you want to, challenge the food. A challenge would consist of a re-introduction of the food once suspected symptoms have resolved. This challenge can also help determine severity of the allergy; as addressed in the above blog article. Some people react to any and all minute derivatives or cross contamination of the allergen, some can handle derivatives or oils, etc. The only true way to know is to challenge, and in the meantime- question everything.
Tuesday, June 7, 2011
FPIES: Video Tributes
FPIES is currently a clinical diagnosis based on symptoms. There is currently no test for it. The diagnosis has come a long way since this mother created this video: FPIES: Not your typical food allergy. A video created by a mom desperate for help and answers to her sons violent reactions. It is the graphic video of her son having a reaction.
Awareness has grown since this video was made, in large parts likely due to her putting the video on YouTube for others to learn and share. I know it was educational for me and my family with our son's reactions because nothing could have captured it better than if we had recorded one ourselves. Thankfully a challenge such as this, that would have been the diagnostic criteria a few years ago, is not needed with the increase in awareness and better understanding of this Non-IgE Allergy. With an experienced MD, a history of symptoms and reactions is often sufficient for this clinical diagnosis. Removal of the offending protein(s) with resolution of symptoms also confirms the diagnosis. It is hopeful that, wth further research, there may one day be diagnostic tools available for this type of food allergy.
I was inspired by the knowledge gained from this mom's experience, I wanted to share our own FPIES story- in hopes that it too, could help another family along this road. Where the above video captures an FPIES to shock reaction, our video highlights pictures of our son's first 2 years. It outlines our struggles in our son's "atypical" FPIES responses. It can be viewed here.
Awareness has grown since this video was made, in large parts likely due to her putting the video on YouTube for others to learn and share. I know it was educational for me and my family with our son's reactions because nothing could have captured it better than if we had recorded one ourselves. Thankfully a challenge such as this, that would have been the diagnostic criteria a few years ago, is not needed with the increase in awareness and better understanding of this Non-IgE Allergy. With an experienced MD, a history of symptoms and reactions is often sufficient for this clinical diagnosis. Removal of the offending protein(s) with resolution of symptoms also confirms the diagnosis. It is hopeful that, wth further research, there may one day be diagnostic tools available for this type of food allergy.
I was inspired by the knowledge gained from this mom's experience, I wanted to share our own FPIES story- in hopes that it too, could help another family along this road. Where the above video captures an FPIES to shock reaction, our video highlights pictures of our son's first 2 years. It outlines our struggles in our son's "atypical" FPIES responses. It can be viewed here.
Saturday, May 14, 2011
Food Allergy Awareness week 2011
We are nearing the end of Food Allergy Awareness week. I have been taking some time to raise awareness on Non-IgE Food Allergy. Non-IgE involves the immune system but in a different way then typical (IgE) allergy. The effects are not as immediate but can be just as serious.
I have become involved in a foundation for Protein Intolerant Children (PIC). Our website is located here: The PIC Foundation where "Our mission is to improve the lives of protein intolerant children and their families by providing information, resources, support forums, and by promoting public awareness and supporting medical research." We also have a facebook page, to utilize the social media to help raise awareness and support for families and can be found here: PIC Facebook page where you will find the article our foundation wrote, and are utilizing to raise awareness on Non-IgE Food Allergy. Help us raise awareness and share the information! Medical journal article references are listed if more information is needed (for yourself or your doctor).
I have become involved in a foundation for Protein Intolerant Children (PIC). Our website is located here: The PIC Foundation where "Our mission is to improve the lives of protein intolerant children and their families by providing information, resources, support forums, and by promoting public awareness and supporting medical research." We also have a facebook page, to utilize the social media to help raise awareness and support for families and can be found here: PIC Facebook page where you will find the article our foundation wrote, and are utilizing to raise awareness on Non-IgE Food Allergy. Help us raise awareness and share the information! Medical journal article references are listed if more information is needed (for yourself or your doctor).
Sunday, April 3, 2011
Research Studies on Non-IgE Allergy
We recently took my son to be involved in a research study at the PCRCD.
Dr.Jyonouchi runs this clinic and her current research is: Th cell polarization and candida reactivity in autistic children with food allergy. It is described: "Our previous study has shown that a high percentage of ASD children with GI symptoms reveal evidence of non IgE mediated, delayed type food allergy (NFA) against common dietary proteins (DPs) and their clinical features are similar to those in non-ASD children with NFA. In infants, the gut immune system is immature and oral tolerance develops slowly during the first 2-3 years of life. Thus, most non-ASD/NFA children outgrow this condition by 3-4 years of age. However, ASD/NFA children appear to require a longer time to outgrow NFA, indicating a possibility that ASD/NFA children have immune abnormalities rendering them more reactive to ‘harmless’ luminal antigens (food and commensal flora.) In this study, we thus hypothesize that dysregulated gut mucosal immune homeostasis is associated with altered innate immune responses that affects development of T-helper (Th) subsets. There are two specific aims for the current study: (1) Assessment of Th cell polarization in ASD children with NFA by intracellular staining of lineage-specific cytokines in Th cells. (2) Assessment of anti-inflammatory Th cell responses in ASD children with NFA by measuring production of counter-regulatory cytokines in response to specific luminal Ag
Dr.Jyonouchi has studied the effects of Non-IgE food allergy (by immune mechanisms to food proteins as described above) with populations of Autistic Spectrum disorders, as well as Inflammatory Bowel Diseases. She describes Non-IgE food allergy in her paper: Non-IgE Food Allergy.
Dr.Jyonouchi concludes much of her findings for treatment around gut homeostasis, and notes in this Pediatric Allergy and Immunology article that "it is crucial for gut mucousal immmune system to establish immune homeostasis that permits us to 1). cohabit with commensal flora under a mutual benefiical relationship, 2). digest huge amounts of macronutrients without provoking immune reactions (oral tolerance), and 3). maintain effective immune defense against pathogens. This somewhat conflicting task may make the gut mucousal immune system error prone, requiring active counter-regulatory measures such as developement of regulatory T (Treg) cells. These measures appear to develop gradually during the first few years of life and this is why infants are prone to be reactive to common dietary proteins in IgE or Non-IgE dependent manner."
I follow her here as much of my own research leads me here as well. While there is much of her research that we can transfer to learn more of FPIES immune responses, mechanisms, gut flora and homeostasis in our own children....but more FPIES-specific research is needed.
Dr.Jyonouchi runs this clinic and her current research is: Th cell polarization and candida reactivity in autistic children with food allergy. It is described: "Our previous study has shown that a high percentage of ASD children with GI symptoms reveal evidence of non IgE mediated, delayed type food allergy (NFA) against common dietary proteins (DPs) and their clinical features are similar to those in non-ASD children with NFA. In infants, the gut immune system is immature and oral tolerance develops slowly during the first 2-3 years of life. Thus, most non-ASD/NFA children outgrow this condition by 3-4 years of age. However, ASD/NFA children appear to require a longer time to outgrow NFA, indicating a possibility that ASD/NFA children have immune abnormalities rendering them more reactive to ‘harmless’ luminal antigens (food and commensal flora.) In this study, we thus hypothesize that dysregulated gut mucosal immune homeostasis is associated with altered innate immune responses that affects development of T-helper (Th) subsets. There are two specific aims for the current study: (1) Assessment of Th cell polarization in ASD children with NFA by intracellular staining of lineage-specific cytokines in Th cells. (2) Assessment of anti-inflammatory Th cell responses in ASD children with NFA by measuring production of counter-regulatory cytokines in response to specific luminal Ag
in comparison with responses to stimuli of innate immunity. Our long-term objective is to assess immune abnormalities associated with oral tolerance in ASD/NFA children. Obtained data are expected to be helpful for identifying risk factors for development of NFA and dysbiosis in autistic children."
(PI: Harumi Jyonouchi, M.D. University of Medicine and Dentistry of New Jersey-New Jersey Medical School.)
Our son, and the other FPIES children that are going there are among her "control" group. The Non-IgE Food Allergy children without ASD (autism spectrum disorder).
Dr.Jyonouchi has done a few studies of this nature. In the study, she tests for the production of proinflammatory (TNF-a, IFN-g, IL-5, IL-12) and counter-regulatory (Il-10, IL-17, TGF-b, ) cytokines production to milk (whey and casein), soy, wheat (gliadin), as well as Candida. The results can help determine classic, chronic, aytpical FPIES responses to these proteins; but mostly it can help determine where in these mechanisms the "break down" is. Does your child have too strong proinflammatory cytokine responses? Treating every protein as foreign and launching attacks of inflammatory mediators? Does the body respond with proinflammatory mediators only to lack sufficient counter regulatory cytokines? Does the body produce minimal proinflammatory mediators but then over-react with counter-regulatory cytokines? It can define more of what is happening at this cellular level. Past research has led to the T-cell mechanism of a Non-IgE food allergy; these tests help define that- with dairy, soy, wheat proteins. Our son, and the other FPIES children that are going there are among her "control" group. The Non-IgE Food Allergy children without ASD (autism spectrum disorder).
Dr.Jyonouchi has studied the effects of Non-IgE food allergy (by immune mechanisms to food proteins as described above) with populations of Autistic Spectrum disorders, as well as Inflammatory Bowel Diseases. She describes Non-IgE food allergy in her paper: Non-IgE Food Allergy.
Dr.Jyonouchi concludes much of her findings for treatment around gut homeostasis, and notes in this Pediatric Allergy and Immunology article that "it is crucial for gut mucousal immmune system to establish immune homeostasis that permits us to 1). cohabit with commensal flora under a mutual benefiical relationship, 2). digest huge amounts of macronutrients without provoking immune reactions (oral tolerance), and 3). maintain effective immune defense against pathogens. This somewhat conflicting task may make the gut mucousal immune system error prone, requiring active counter-regulatory measures such as developement of regulatory T (Treg) cells. These measures appear to develop gradually during the first few years of life and this is why infants are prone to be reactive to common dietary proteins in IgE or Non-IgE dependent manner."
I follow her here as much of my own research leads me here as well. While there is much of her research that we can transfer to learn more of FPIES immune responses, mechanisms, gut flora and homeostasis in our own children....but more FPIES-specific research is needed.
Wednesday, March 23, 2011
Allergy Nutrition
I first published this post on my blog last September, when I began to do further research into my son's FPIES. I started with Allergy, with one of my favorite resources at that time (remaisn a top resource):
Vickerstaff Health Services
Janice Joneja Vickerstaff, PhD, RD is an inspiration for me. I had the privilege of hearing her speak at a Nutritional Peds conference a few years ago, her discussion on allergy’s intrigued and inspired me. I bought one of her books on “Dealing with Food Allergies in Babies and Children” right away, and hungry for more information, I also bought another one of her Allergy books. I have also since bought Digestion, Diet, and Disease to learn more about gut health from her perspective. I find her books very easy to read and follow, and full of valid medical information; so have utilized it as a resource time and again.
I’d like to explain more, from my understanding of her books. I will be using her words for much of it but not always directly quoting all of it- I merely want to provide an overview/synopsis/outline of the pertinent information to this “type” of allergy.
“Reasons that one child’s body responds to food by developing distressing symptoms and another uses the same food for comfort and nurture may be found in several factors”.
1. Child’s inherited genetic make up.
2. Circumstances within first food encounter
3. Microorganisms that live in child’s GI tract
4. Medications take by mouth, or exposed to (such as mothers milk)
5. Other factors research is only beginning to understand.
“Food sensitivity is unlike any other disease entity….any food is capable of triggering an allergic reaction to a child who has been sensitized to it, or lacks the systems required to process it adequately when it enters the body”.
What is the mechanism for food allergy? And how could this relate to FPIES?
When an allergen enters the body of a person at risk for allergy, an extremely complex series of events “set in motion that will finally result in the release of chemical (called inflammatory mediators) that act on body tissue to cause the symptoms of allergy. All immunological processes involve the various white blood cells (leukocytes), and different type of chemicals they produce”.
First step: the body recognizes the invading antigen. “An antigen is a protein within the cells of any living material that enters the body. When an antigen causes an immune response, it is an allergen. When the antigen enters the body, the white blood cells (lymphocytes) are activated. Lymphocytes are the first cells of the immune system that recognize and respond to anything foreign entering the body (sentinels of the immune system)”. There are two types of Lymphocytes in the blood: Tcells and Bcells. Tcells are the ultimate gatekeepers and controllers of the immune system. “Th (helper T cells) are responsible for identifying foreign materials that enter the body. Th cells initiate and direct the subsequent activities of the immune system if foreign material is deemed a threat…. T Cells exert control by means of messenger chemicals, cytokines”.
The response to cytokines is Th1 or Th2 and this response controls the way the body reacts. “When a pathogen (disease causing microorganism- virus, bacteria, other foreign material) enters, the immune system protects the body by a Th1 response (IgG). Cytokines are produced and stimulate the formation of antibodies of the IgG class which destroy the invading microorganisms by means of the complement cascade…symptoms such as fever, aching muscles, fatigue, malaise (much like the flu) are the result of the body’s response to cytokines and other inflammatory mediators produced during this battle between the immune system and foreign invader”. “The complement cascade is a group of over 20enzymatic proteins in the blood that act together in response to antigen and antibody to destroy foreign cells by splitting them apart (lysis); this process releases various chemical byproducts that act on opsonin’s, chemotoxins, and anaphlatoxins to help destroy a threat to the body and results in inflammation in various tissues.”
So, if FPIES is an IgG response, it is the Th1 response that is activated. It sees the food as a foreign substance – in the same way it would see and attack a virus or bacteria.
Th1 response protects the body from disease, and the IgG antibodies are responsible for the ultimate destruction of the invader. The Th2 response results in allergy, IgE antibody.
So, if Th1 is the first line of defense against IgE, FPIES is an overreactive Th1 response
Some evidence that allergy is inherited… “the characteristic inherited is the potential to respond with a Th2 response when harmless foreign materials enter the body…. Some suggest Th2 is more primitive response than Th1 and as baby matures, the potential for immune system to respond with Th2 is gradually diminished. This decline, together with the maturation of the digestive tract (that provides a barrier between food molecules and immune cells) would explain why children outgrow their allergies”.
What is Oral Tolerance? “Oral tolerance is a term to indicate that although the immune system of the digestive tract can recognize that all the material we consume as food is completely foreign to our bodies, a tolerizing event has occurred that has taught the T cells that the foreign material is harmless and can safely enter the body”.
Something is askew in the FPIES child that the T cells perceive this as a harmful substance; they are taught to remember that it was originally perceived as a harmful substance; each subsequent ingestion has more T cell memory (army) to fight this perceived invader.
All food is foreign to the body (upon first ingestions)….what is it that allows food to apparently evade the barriers of the immune system in a normal child vs. an FPIES child that food is perceived as invaders to the immune system?
Immune System and Digestive Tract
The Immune system of the GI is different than other parts of the body, it is called the GALT- Gut Associated Lymphoid Tissue. “Processing of food through this system allows the uptake of nutrients through the digestive tract walls without triggering the protective response that would otherwise form a barrier to the foreign materials in food. At the same time- any virus or bacteria taken in through the digestive tract are effectively excluded by the GALT. We have a system that can- at the same time and in the same place- recognize and differentiate foreign materials that is safe (food) and foreign material that is a threat (microorganism, toxins….).”
So, is FPIES a breakdown in the GALT? A deficiency mechanism, or an over reactive one?
“But that isn’t the whole story, the GALT must also distinguish between invading microorganisms and other permanent residents of the large intestine- gut microflora”. And many moms have suspected/known their little one’s microflora is “off”. “Microorganisms in the large intestine defend the bowel from invasion by harmful microorganisms by competing with them for space and nutrients; also keeping surrounding tissue healthy by stimulating the GALT in a positive manner”.
Process of Tolerance:
“The process of oral tolerance involves the T cells and their “messenger chemicals” cytokines. T cells that first encounter the foreign food when it enters the very first time (breast milk or solid foods) are of the Th1 type (Th3 immunological protection). Food molecules are picked up by special cells in the infants digestive tract. The antigenic parts of the food (proteins) are then “presented” to the T cells where they couple of special receptor molecules on the T cell surface”.
“T cells with attached food molecules are then transported on the lymphatic system to the thymus gland. There, the regulatory T cells (Treg) stop any further action on the part of the Th1 cells when it is discovered that the “foreign molecules” pose no threat to the body. This process of inhibiting T cell action is carried out by cytokines especially TGFβ(Transforming Growth Factor-Beta) and possibly IL-10 (Interlukein 10).”
Is there a deficiency in the cytokines (such as tumor necrosis factor, transforming growth factor, or IL-10) that inhibits this regulation to happen in the FPIES child?
“The ‘educated’ T cells are then transported in the blood circulatory system and back into the digestive tract GALT as “memory cells”. Is this where the reactions become full body? Eczema, itching, thrombocytosis, angioedema, etc. leading up to a trigger reaction, as the T cells make their way through the body and back to the GALT and now have memory cells to attack with future ingestion's (the delayed-“build” response some of us see)?
FPIES is a Th1 response- the body sees food proteins the same as disease causing microorganisms ; there is a skew in FPIES kids bodies T cell response- Th1 is OVER REACTIVE!
IgE allergy = B cell lymphocytes= Th2 response =produce IgE antibodies
Non IgE = T cell= over reactive and does not proceed to Th2 response (thus preventing IgE food allergy- actually protecting the body- as it does for viruses/bacteria).
FPIES is a skew/”mis-fire” of the Tcell action….the food proteins should be going through the Th1 as “foreign but safe” and to the Th2 responses and either producing antibodies (IgE) or continue on as safe (already passing Th1 gate keepers). But with FPIES, the food proteins go through the Th1 response and get picked up there as foreign and perceived threats; the immune response is not initiated because it is begun in the non-immune Th1 response- it is attacked before it gets to the Th2!
-White blood cells aid the immune system in recognizing foreign proteins.
-T helper cells produce characteristic cytokines.
-Specific cytokines determine response – Th1 protection vs. Th2 Allergy vs. Th3 Oral tolerance
Food = white blood cells recognition =Lymphocyte = T cells= Th cells= cytokines= protection vs. allergy. FPIES is a disruption in the Th1/Th2 response.
Antibodies in food allergy
IgE= recognized typical food allergy response, but there are other antibodies in food sensitivity. IgG is being recognized in Celiac gluten sensitive individuals. IgG is also thought to be what FPIES response is related to, although isolating the specific levels with other factors has not been achieved for FPIES. IgG is not yet a reliable test for food allergy.
“IgG antibody can be found circulating in the blood of people who have no signs or history of adverse reaction to foods. In fact, some think that an increase in anti-food IgG in some cases may be indicative of successful resolution of IgE mediated allergy. IgG mediated allergy remains complicated because of the nature of the antibody and the immunological reactions associated with it”.
Present knowledge (IgG):
-4 classes: IgG1, IgG2, IgG3, IgG4
-IgG4 subclass high affinity for food antigens
-IgG4 may be associated with milk allergy, in particular milk protein B-lactoglobin in atopic dermatitis (eczema) in children.
-Some evidence that total (all 4 classes measured together) might represent some protection from IgE
(again showing that a good IgG response is actually protective for IgE allergy)
-Food allergy in infants frequently associated with increased gut permeability “leaky gut”
Leaky Gut
"Antigenic food molecules passing into circulation trigger production of anti-food IgG. Thus, in cases of IgE-mediated food allergy that results in inflammatory reactions within the GI tract causing non-intact digestive epithelium, it is logical to expect to find higher than normal levels of anti-food IgG. Some think that these anti-food IgG antibodies represent a protective mechanism, rather than a source of allergic pathway”.
Conditions that predispose to allergy:
1. Immaturity of Infants Immune System – Immune system elements are in place at birth but do not function at levels to provide adequate protection against all infection. Antibodies are a fraction of an adults and secretory IgA (sIgA) the first line of defense of mucous membranes is absent at birth. Babies can have impaired or delayed maturing of various functions including cytokine production.
2. Permeability of digestive tract “leaky gut” – Infants intestines are highly permeable particularly 6-12mo.(become mature by 3yrs) and can absorb large molecules of foods that trigger the Th2 response.
3. Breast feeding – “breast milk provides the ideal nutritional, immunological, and physiologic nourishment for all newborns. Components of human milk enhance the baby’s natural defense and promote maturation of the immune system”. There is data that indicates the breast milk of atopic (allergic)mothers differs immunologically from that of non-allergic mothers. Atopic mothers tend to have higher levels of the cytokines and chemokines associated with allergy in their breastmilk. In addition, they tend to have a lower level of cytokines known as transforming growth factor (TGF-B) that promotes tolerances of food components in the intestinal immune response.
Vickerstaff Health Services
Janice Joneja Vickerstaff, PhD, RD is an inspiration for me. I had the privilege of hearing her speak at a Nutritional Peds conference a few years ago, her discussion on allergy’s intrigued and inspired me. I bought one of her books on “Dealing with Food Allergies in Babies and Children” right away, and hungry for more information, I also bought another one of her Allergy books. I have also since bought Digestion, Diet, and Disease to learn more about gut health from her perspective. I find her books very easy to read and follow, and full of valid medical information; so have utilized it as a resource time and again.
I’d like to explain more, from my understanding of her books. I will be using her words for much of it but not always directly quoting all of it- I merely want to provide an overview/synopsis/outline of the pertinent information to this “type” of allergy.
“Reasons that one child’s body responds to food by developing distressing symptoms and another uses the same food for comfort and nurture may be found in several factors”.
1. Child’s inherited genetic make up.
2. Circumstances within first food encounter
3. Microorganisms that live in child’s GI tract
4. Medications take by mouth, or exposed to (such as mothers milk)
5. Other factors research is only beginning to understand.
“Food sensitivity is unlike any other disease entity….any food is capable of triggering an allergic reaction to a child who has been sensitized to it, or lacks the systems required to process it adequately when it enters the body”.
What is the mechanism for food allergy? And how could this relate to FPIES?
When an allergen enters the body of a person at risk for allergy, an extremely complex series of events “set in motion that will finally result in the release of chemical (called inflammatory mediators) that act on body tissue to cause the symptoms of allergy. All immunological processes involve the various white blood cells (leukocytes), and different type of chemicals they produce”.
First step: the body recognizes the invading antigen. “An antigen is a protein within the cells of any living material that enters the body. When an antigen causes an immune response, it is an allergen. When the antigen enters the body, the white blood cells (lymphocytes) are activated. Lymphocytes are the first cells of the immune system that recognize and respond to anything foreign entering the body (sentinels of the immune system)”. There are two types of Lymphocytes in the blood: Tcells and Bcells. Tcells are the ultimate gatekeepers and controllers of the immune system. “Th (helper T cells) are responsible for identifying foreign materials that enter the body. Th cells initiate and direct the subsequent activities of the immune system if foreign material is deemed a threat…. T Cells exert control by means of messenger chemicals, cytokines”.
The response to cytokines is Th1 or Th2 and this response controls the way the body reacts. “When a pathogen (disease causing microorganism- virus, bacteria, other foreign material) enters, the immune system protects the body by a Th1 response (IgG). Cytokines are produced and stimulate the formation of antibodies of the IgG class which destroy the invading microorganisms by means of the complement cascade…symptoms such as fever, aching muscles, fatigue, malaise (much like the flu) are the result of the body’s response to cytokines and other inflammatory mediators produced during this battle between the immune system and foreign invader”. “The complement cascade is a group of over 20enzymatic proteins in the blood that act together in response to antigen and antibody to destroy foreign cells by splitting them apart (lysis); this process releases various chemical byproducts that act on opsonin’s, chemotoxins, and anaphlatoxins to help destroy a threat to the body and results in inflammation in various tissues.”
So, if FPIES is an IgG response, it is the Th1 response that is activated. It sees the food as a foreign substance – in the same way it would see and attack a virus or bacteria.
Th1 response protects the body from disease, and the IgG antibodies are responsible for the ultimate destruction of the invader. The Th2 response results in allergy, IgE antibody.
So, if Th1 is the first line of defense against IgE, FPIES is an overreactive Th1 response
Some evidence that allergy is inherited… “the characteristic inherited is the potential to respond with a Th2 response when harmless foreign materials enter the body…. Some suggest Th2 is more primitive response than Th1 and as baby matures, the potential for immune system to respond with Th2 is gradually diminished. This decline, together with the maturation of the digestive tract (that provides a barrier between food molecules and immune cells) would explain why children outgrow their allergies”.
What is Oral Tolerance? “Oral tolerance is a term to indicate that although the immune system of the digestive tract can recognize that all the material we consume as food is completely foreign to our bodies, a tolerizing event has occurred that has taught the T cells that the foreign material is harmless and can safely enter the body”.
Something is askew in the FPIES child that the T cells perceive this as a harmful substance; they are taught to remember that it was originally perceived as a harmful substance; each subsequent ingestion has more T cell memory (army) to fight this perceived invader.
All food is foreign to the body (upon first ingestions)….what is it that allows food to apparently evade the barriers of the immune system in a normal child vs. an FPIES child that food is perceived as invaders to the immune system?
Immune System and Digestive Tract
The Immune system of the GI is different than other parts of the body, it is called the GALT- Gut Associated Lymphoid Tissue. “Processing of food through this system allows the uptake of nutrients through the digestive tract walls without triggering the protective response that would otherwise form a barrier to the foreign materials in food. At the same time- any virus or bacteria taken in through the digestive tract are effectively excluded by the GALT. We have a system that can- at the same time and in the same place- recognize and differentiate foreign materials that is safe (food) and foreign material that is a threat (microorganism, toxins….).”
So, is FPIES a breakdown in the GALT? A deficiency mechanism, or an over reactive one?
“But that isn’t the whole story, the GALT must also distinguish between invading microorganisms and other permanent residents of the large intestine- gut microflora”. And many moms have suspected/known their little one’s microflora is “off”. “Microorganisms in the large intestine defend the bowel from invasion by harmful microorganisms by competing with them for space and nutrients; also keeping surrounding tissue healthy by stimulating the GALT in a positive manner”.
Process of Tolerance:
“The process of oral tolerance involves the T cells and their “messenger chemicals” cytokines. T cells that first encounter the foreign food when it enters the very first time (breast milk or solid foods) are of the Th1 type (Th3 immunological protection). Food molecules are picked up by special cells in the infants digestive tract. The antigenic parts of the food (proteins) are then “presented” to the T cells where they couple of special receptor molecules on the T cell surface”.
“T cells with attached food molecules are then transported on the lymphatic system to the thymus gland. There, the regulatory T cells (Treg) stop any further action on the part of the Th1 cells when it is discovered that the “foreign molecules” pose no threat to the body. This process of inhibiting T cell action is carried out by cytokines especially TGFβ(Transforming Growth Factor-Beta) and possibly IL-10 (Interlukein 10).”
Is there a deficiency in the cytokines (such as tumor necrosis factor, transforming growth factor, or IL-10) that inhibits this regulation to happen in the FPIES child?
“The ‘educated’ T cells are then transported in the blood circulatory system and back into the digestive tract GALT as “memory cells”. Is this where the reactions become full body? Eczema, itching, thrombocytosis, angioedema, etc. leading up to a trigger reaction, as the T cells make their way through the body and back to the GALT and now have memory cells to attack with future ingestion's (the delayed-“build” response some of us see)?
FPIES is a Th1 response- the body sees food proteins the same as disease causing microorganisms ; there is a skew in FPIES kids bodies T cell response- Th1 is OVER REACTIVE!
IgE allergy = B cell lymphocytes= Th2 response =produce IgE antibodies
Non IgE = T cell= over reactive and does not proceed to Th2 response (thus preventing IgE food allergy- actually protecting the body- as it does for viruses/bacteria).
FPIES is a skew/”mis-fire” of the Tcell action….the food proteins should be going through the Th1 as “foreign but safe” and to the Th2 responses and either producing antibodies (IgE) or continue on as safe (already passing Th1 gate keepers). But with FPIES, the food proteins go through the Th1 response and get picked up there as foreign and perceived threats; the immune response is not initiated because it is begun in the non-immune Th1 response- it is attacked before it gets to the Th2!
-White blood cells aid the immune system in recognizing foreign proteins.
-T helper cells produce characteristic cytokines.
-Specific cytokines determine response – Th1 protection vs. Th2 Allergy vs. Th3 Oral tolerance
Food = white blood cells recognition =Lymphocyte = T cells= Th cells= cytokines= protection vs. allergy. FPIES is a disruption in the Th1/Th2 response.
Antibodies in food allergy
IgE= recognized typical food allergy response, but there are other antibodies in food sensitivity. IgG is being recognized in Celiac gluten sensitive individuals. IgG is also thought to be what FPIES response is related to, although isolating the specific levels with other factors has not been achieved for FPIES. IgG is not yet a reliable test for food allergy.
“IgG antibody can be found circulating in the blood of people who have no signs or history of adverse reaction to foods. In fact, some think that an increase in anti-food IgG in some cases may be indicative of successful resolution of IgE mediated allergy. IgG mediated allergy remains complicated because of the nature of the antibody and the immunological reactions associated with it”.
Present knowledge (IgG):
-4 classes: IgG1, IgG2, IgG3, IgG4
-IgG4 subclass high affinity for food antigens
-IgG4 may be associated with milk allergy, in particular milk protein B-lactoglobin in atopic dermatitis (eczema) in children.
-Some evidence that total (all 4 classes measured together) might represent some protection from IgE
(again showing that a good IgG response is actually protective for IgE allergy)
-Food allergy in infants frequently associated with increased gut permeability “leaky gut”
Leaky Gut
"Antigenic food molecules passing into circulation trigger production of anti-food IgG. Thus, in cases of IgE-mediated food allergy that results in inflammatory reactions within the GI tract causing non-intact digestive epithelium, it is logical to expect to find higher than normal levels of anti-food IgG. Some think that these anti-food IgG antibodies represent a protective mechanism, rather than a source of allergic pathway”.
Conditions that predispose to allergy:
1. Immaturity of Infants Immune System – Immune system elements are in place at birth but do not function at levels to provide adequate protection against all infection. Antibodies are a fraction of an adults and secretory IgA (sIgA) the first line of defense of mucous membranes is absent at birth. Babies can have impaired or delayed maturing of various functions including cytokine production.
2. Permeability of digestive tract “leaky gut” – Infants intestines are highly permeable particularly 6-12mo.(become mature by 3yrs) and can absorb large molecules of foods that trigger the Th2 response.
3. Breast feeding – “breast milk provides the ideal nutritional, immunological, and physiologic nourishment for all newborns. Components of human milk enhance the baby’s natural defense and promote maturation of the immune system”. There is data that indicates the breast milk of atopic (allergic)mothers differs immunologically from that of non-allergic mothers. Atopic mothers tend to have higher levels of the cytokines and chemokines associated with allergy in their breastmilk. In addition, they tend to have a lower level of cytokines known as transforming growth factor (TGF-B) that promotes tolerances of food components in the intestinal immune response.
New Guidelines for the Diagnosis and Management of Food Allergy in the United States
In December of 2010, the New Guidelines for Diagnosis and Management of Food Allergy in the US was released from the National Institute of Allergy and Infectious Disease, a component of the National Institute of Health. The guidelines were developed over a 2yr.period with combined efforts from an Expert Panel from 34 professional organizations, federal agencies,and patient advocacy groups. The full report can be viewed here: The Journal of Allergy and Clinical Immunology
The full report is 84 pages long. The first glance I took of it, of course I skipped through to where it mentions FPIES. Yes, that is right- it gives an entire section for FPIES. It is a very real diagnosis and having it mentioned here in the new guidelines for food allergies is a big step for the future of these children affected by it. But the report is, of course, not limited to FPIES. I have begun to read through it and am impressed with the information it provides, updated information that is needed as this country's food allergies are on the rise daily. In fact, that is one of the reasons they developed the new guidelines.
The first thing I notice is in Section 2 (pg7): Definitions "A food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food." This is updated terminology to address both IgE and Non-IgE food allergies. Typical immediate onset allergies are IgE, that is IgE-mediated mechanisms are involved. Non-IgE are delayed and thought to typically involve cellular mechanisms. "The terms Allergy and Allergic Disease are broadly encompassing and include clinical conditions associated with altered immunologic reactivity that may be either IgE mediated or non-IgE mediated".
It goes on to describe terms such as Food Allergen, this addresses foods or specific ingredients and components in a food (typically proteins). It also addresses cross-reactivity definition and significance in food allergy. Food oils are considered low allergenicity if virtually all food proteins have been removed in processing (note low, not non-allergenicity).
I am pleased to see that there is a lot of language in this report to describe diagnosing food allergy- not limited to serum levels of IgE, but in response to tried-and-true elimination and challenge of the foods. Things to be considered is the level of reaction, the quality of life - the balance of benefit and harm..."identification and avoidance of foods responsible for food-induced allergic reactions improve quality of life and potentially prevent life-threatening reactions and disorders. With the appropriate evaluation, there is a low risk of erroneously diagnosing someone as food allergic and adversely affecting his or her nutritional well-being and social interactions".
This is an important moving forward (and over due) step in the world of Food Allergy. And as not only a mom of an FPIES child, but a Dietetic professional as well, this is of critical importance -- to properly recognize, diagnosis and treat food allergy's not only so that diets are not over restrictive but also, on the other end of the spectrum, so that proper identification to symptoms can be made, and treated with removal of the offending food(s). This is important because as of now, allergy's are only considered "true" if they produce an IgE and immediate immunological response. These guidelines are helping to redefine, and hopefully reshape how adverse reactions to foods are viewed, and thus diagnosed and treated. It is very important to be able to treat so many growing number of protein intolerant infants and toddlers, to have recognition that not all food allergies are IgE response, that Non-IgE food allergy's exist, are prevalent and a significant adverse health effect on children suffering from them.
Food Protein Induced Enterocolitis (FPIES) and Food Protein induced allergic proctocolitis (AP) are initially described on the bottom of page 8.
A table (in section 4, pg 20) for "Diagnosis of food allergy: when should a food allergy be suspected?" and includes delayed GI reactions as well as other cutaneous, ocular, and respiratory delayed symptoms (as part of the cascade of symptoms)- it should be noted that the expert panel notes that food allergy rarely causes isolated respiratory symptoms such as asthma and allergic rhinitis.
Included in section 4 (page 22) is an outline for Differential for Diagnosis of Food Allergy, which include addressing adverse reactions to foods that are not allergenic in origin.
A few pages later (page 27) is the discussion on Diagnosis of non-IgE-mediated immunologic adverse reactions to food. This is where FPIES and AP are described as Guideline for diagnosis, rationale and the balance of benefit and harms. It is a good synopsis of the research on FPIES thus far. I am happy to see it has it's place here and described so well for the clinicians. There are additional research articles on FPIES, and additional research is being done to further understand this diagnosis, and ultimately (hopefully) find better treatment options to provide to the families struggling with a severe protein intolerant child.
It covers a lot of new language, encompasses newer research on Non-IgE allergies, as well as clarifications on IgE reactions. In general, it is well written report and hopeful that with FPIES and AP being included; it will begin to be in the differential diagnosis for more kids presenting to the doctors offices with feeding intolerance's.
The full report is 84 pages long. The first glance I took of it, of course I skipped through to where it mentions FPIES. Yes, that is right- it gives an entire section for FPIES. It is a very real diagnosis and having it mentioned here in the new guidelines for food allergies is a big step for the future of these children affected by it. But the report is, of course, not limited to FPIES. I have begun to read through it and am impressed with the information it provides, updated information that is needed as this country's food allergies are on the rise daily. In fact, that is one of the reasons they developed the new guidelines.
The first thing I notice is in Section 2 (pg7): Definitions "A food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food." This is updated terminology to address both IgE and Non-IgE food allergies. Typical immediate onset allergies are IgE, that is IgE-mediated mechanisms are involved. Non-IgE are delayed and thought to typically involve cellular mechanisms. "The terms Allergy and Allergic Disease are broadly encompassing and include clinical conditions associated with altered immunologic reactivity that may be either IgE mediated or non-IgE mediated".
It goes on to describe terms such as Food Allergen, this addresses foods or specific ingredients and components in a food (typically proteins). It also addresses cross-reactivity definition and significance in food allergy. Food oils are considered low allergenicity if virtually all food proteins have been removed in processing (note low, not non-allergenicity).
I am pleased to see that there is a lot of language in this report to describe diagnosing food allergy- not limited to serum levels of IgE, but in response to tried-and-true elimination and challenge of the foods. Things to be considered is the level of reaction, the quality of life - the balance of benefit and harm..."identification and avoidance of foods responsible for food-induced allergic reactions improve quality of life and potentially prevent life-threatening reactions and disorders. With the appropriate evaluation, there is a low risk of erroneously diagnosing someone as food allergic and adversely affecting his or her nutritional well-being and social interactions".
This is an important moving forward (and over due) step in the world of Food Allergy. And as not only a mom of an FPIES child, but a Dietetic professional as well, this is of critical importance -- to properly recognize, diagnosis and treat food allergy's not only so that diets are not over restrictive but also, on the other end of the spectrum, so that proper identification to symptoms can be made, and treated with removal of the offending food(s). This is important because as of now, allergy's are only considered "true" if they produce an IgE and immediate immunological response. These guidelines are helping to redefine, and hopefully reshape how adverse reactions to foods are viewed, and thus diagnosed and treated. It is very important to be able to treat so many growing number of protein intolerant infants and toddlers, to have recognition that not all food allergies are IgE response, that Non-IgE food allergy's exist, are prevalent and a significant adverse health effect on children suffering from them.
Food Protein Induced Enterocolitis (FPIES) and Food Protein induced allergic proctocolitis (AP) are initially described on the bottom of page 8.
A table (in section 4, pg 20) for "Diagnosis of food allergy: when should a food allergy be suspected?" and includes delayed GI reactions as well as other cutaneous, ocular, and respiratory delayed symptoms (as part of the cascade of symptoms)- it should be noted that the expert panel notes that food allergy rarely causes isolated respiratory symptoms such as asthma and allergic rhinitis.
Included in section 4 (page 22) is an outline for Differential for Diagnosis of Food Allergy, which include addressing adverse reactions to foods that are not allergenic in origin.
A few pages later (page 27) is the discussion on Diagnosis of non-IgE-mediated immunologic adverse reactions to food. This is where FPIES and AP are described as Guideline for diagnosis, rationale and the balance of benefit and harms. It is a good synopsis of the research on FPIES thus far. I am happy to see it has it's place here and described so well for the clinicians. There are additional research articles on FPIES, and additional research is being done to further understand this diagnosis, and ultimately (hopefully) find better treatment options to provide to the families struggling with a severe protein intolerant child.
It covers a lot of new language, encompasses newer research on Non-IgE allergies, as well as clarifications on IgE reactions. In general, it is well written report and hopeful that with FPIES and AP being included; it will begin to be in the differential diagnosis for more kids presenting to the doctors offices with feeding intolerance's.
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