1. Food Allergies in Infants and Children
Bonnie Proulx, APRN, PNP
Pediatric Gastroenterology
Children’s Hospital at Dartmouth – Manchester, NH

2. Quiz Which patient may have a food allergy?
3 year old with hives and vomiting 15 minutes after eating vanilla ice cream from Baskin Robbins. Child eats ice cream at home with no problems.
46 year old man with episode of syncope 1 hour after eating lobster for dinner. No other symptoms but did complain that he “just didn’t feel right”.
3 month old baby with bloody stools and failure to thrive.
15 year old with chronic, pruritic rash on buttocks and elbows.
25 year old with mouth and lip itching from apples, peaches, and cherries. Cooked fruit causes no symptoms.

3. Answer
ALL OF THE ABOVE
I chose this topic as I get asked at least 100 times a day if the child’s symptoms are from food allergies – I have many children taken to alternative health care providers and come back with laundry lists of “food allergies” so I wanted to review all the literature and be objective today to help you answer this overwhelming question and give you the how/when to evaluate.

4. Food Reactions IgE-mediated Food Allergy Reactions
Oral Allergy Syndrome
Non-IgE-mediated Food Hypersensitivity

5. Food Allergy
Food allergy is characterized by immunologic responses to specific food proteins
Prevalence is greatest in the first few years of life and declines over the first decade.
Clinical manifestations of food allergy are dependent on the immunologic mechanism
IgE-mediated reactions – rapid onset
Non IgE – make take hours or days
It is an ige response - the body is exposed to what it deems harmful – it makes an antibody against that protein and thus the next exposure will cause a reaction

6. Food Allergy
Defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food

7. What It Is Not Chemical/pharmaceutical effect
Caffeine: Tremor, diarrhea, cramps
Tyramine (cheese): Migraines
Scombroid fish poisoning (spoiled fish): histadine -> flush, pruritis, bronchospasm, tachycardia
Sulfites (cheese, wine, beer, dried fruit, lettuce): bronchospasm
MSG
Aspartame
Enzyme deficiency
Lactose/fructose
Malabsorption
Bacterial toxin
Jenny and wine reaction

8. Epidemiology As of 2014, 1 in 13 children has a FA
About 4% of total U.S. population (12 million) has food allergy
6% of children (3 million)
3.5% of adults
Food allergies in U.S. and other industrialized countries is increasing, along with other atopic diseases
Peanut allergy has tripled since 1990
8 foods account for 90% of food allergy in U.S.
Milk, egg, peanut, tree nuts, wheat, soy, fish, and shellfish
Each year, deaths are attributed to food-related anaphylaxis
Reviewed new literature released in january 2015 –and stats still about the same –
Interestingly peanut allergy has tripled since 1990 – etiology unknown
Food allergies rates highest when self reported at 12% but truly approximately 3-6 % with true food testing and challenges with proven diagnostic methods

9. Prevalence Food Children Adults Milk 2.5% 0.3% Egg 1.3% 0.2% Peanut
0.8%
0.6%
Tree Nuts
0.5%
Fish
0.1%
0.4%
Shellfish
2.0%
You can see that milk is the most common in children but not in adults – thus many children outgrowing this with less than 1% by age 8

10. Why Is It Increasing? Hygiene Hypothesis
Food Processing: roasted vs. boiled peanuts
Topical sensitization
Your guess is as good as mine
The hygiene theory believes in parts that smaller families – less exposure to illnesses, over use of antibiotics sterilizing the gut and delaying introduction of solids may be contributing

11. Some food allergies may be “outgrown”
Sometimes “outgrown”
Usually not “outgrown”
Eggs
Milk
Soy
Peanuts
Tree nuts
Fish
Shellfish

12. 90% of food allergies are caused by a limited number of foods
In Children
In Adults
Milk
Egg
Peanuts
Wheat
Soy
Tree nuts
Peanuts
Tree nuts
Fish
Shellfish
We see this in how the diet for kids with eosinophilic esophagitis are approached -

13. Includes immunologic and physiologic barrier Stomach acidity
The gastrointestinal tract has a barrier system to protect the body from ingested antigens
Includes immunologic and physiologic barrier
Stomach acidity
Mucin coat
Gastrointestinal enzymes
Immunoglobulins
The gastrointestinal tract processes ingested food for absorption. It neutralizes foreign antigens and blocks them from entering the circulation. Enzymes from salivary, gastric, pancreatic and intestinal secretions, combined with mastication, gastric acid, and peristalsis, reduce ingested substances to small sugars, peptides and fats. Non-specific (mucin coat) and specific (secretory IgA) mechanisms ‘hold up' and/or block potentially harmful antigenic substances from penetrating the intestinal barrier.

14. Food Allergy: Natural History
Most children will outgrow milk, egg, wheat and soy allergy by school age or adolescence
Wheat: 29% by 4y, 56% by 8y, 65% by 12y
Milk: 80% by 5y
Nut, fish and peanut allergy tend to be life-long
20% of peanut allergic children outgrow peanut allergy, but 8% of these may re-sensitize
These statistics have not really changed as provided by the data from Sampson et al in 2015

15. Children with atopic disease are more likely to have food allergies
Seen in approximately 35% of children with atopic dermatitis.
Moderate to Severe atopic dermatitis have 35% increased risk of food allergy
This is due to the ige e mediated connection or sometime referred to as allergic triad -

16. IgE-Mediated Reactions: Pathophysiology
Bronchoconstriction
Mucous production
Cough receptor
Increased gastric acid secretion
Increased intestinal motility
Increased vascular permeability
Dyspnea
Wheeze
Chest tightness
Cough
Abdominal pain/cramping
Vomiting
Diarrhea

17. IgE-Mediated Reactions: Pathophysiology
Itch receptors
Increased vascular permeability
Tachycardia
Vasodilation
Hypotension
Pruritis
Flush
Urticaria
Angioedema
Syncope
Seizures
Shock
Death

18. IgE-mediated Food Allergy Reactions
Arise when food allergens penetrate the gastrointestinal barrier, initiating the classic immediate hypersensitivity chain of events
Frequently cause acute urticaria/angioedema
May cause life-threatening events without cutaneous responses
Signs/symptoms may occur within minutes to a couple of hours
The most severe cases involve the cardiovascular and/or respiratory systems, resulting in food induced anaphylaxis

19. IgE-Mediated Reactions: Clinical Picture
80-90% reactions involve the skin
Flush
Pruritis
Urticaria
Angioedema
70% reactions involve the GI tract
Nausea/vomiting
Crampy pain
Diarrhea
30-40% reactions involve the respiratory tract
Cough
Wheeze
SOB
Tightness in chest
<10% reactions involve the cardiovascular system
Hypotension
Syncope
Pre-syncope

20. IgE-Mediated Reactions: Clinical Picture
IgE-mediated food allergy very rarely causes chronic symptoms
Asthma and rhinitis can occur acutely as part of a reaction, but chronic rhinitis and respiratory symptoms in absence of other signs or symptoms of a systemic reaction are not typically due to food
Chronic abdominal pain or diarrhea may be due to IgE-mediated food allergy but other causes, especially in an otherwise non-atopic patient, are much more common
Chronic urticaria is rarely found to be caused by food or food additives, in spite of extensive testing

21. Diagnosing Food Allergy
Patient history is paramount in the selection of foods for testing
Consider:
Types of symptom expressed
Relationship between symptom onset and ingestion
Time since the last reaction
Quantity of suspected food ingested when symptoms occurred
Activities at the time of (or prior to) symptoms

22. Diagnosing Food Allergy
Patient history is paramount in the selection of foods for testing
Skin testing is useful
In vitro tests (ELISA) are recommended for pts with:
Significant dermatographism
Severe skin disease and limited surface area for skin testing
Suspected marked sensitivities to certain foods
Difficulty in discontinuing antihistamines or certain antidepressants
Doctors generally start the testing process with a skin test or a blood test. The prick skin test, which is also known as the scratch test, examines the patient's reaction to a solution containing a protein that triggers allergies.
The doctor places a drop of the substance on the patient's arm or back. The doctor then uses a needle to prick or scratch the skin. This allows the potential allergen to enter the patient's skin. If more than one food allergy is suspected, the test is repeated with other proteins applied to the skin. After about 15 minutes, the doctor can read the reactions on the patient's skin.
If there is no reaction, the patient is probably not allergic to that food. The possibility of an allergy is indicated by the presence of a wheal, a bump that resembles a mosquito bite. The wheal signifies a positive reaction to the test. However, the test may show a false positive, which is a reaction to a food that does not cause allergies.
The skin test is not appropriate for people who are severely allergic or have skin conditions like eczema. Those people are given the RAST (radioallergosorbent test). This test measures the presence of food-specific IgE in the blood. After a sample of the patient's blood is taken, it is sent to a laboratory. The sample is tested with different foods. Levels of antibodies are measured, and the reactions to different proteins are ranked. While measurement systems may vary, a high ranking indicates a high number of antibodies. Lab results are generally completed within a week.
Results to this test may not be conclusive. A negative test may not have identified antibodies in the patient's blood. Positive results make it probable but not definite that the patient has allergies.

23. IgE-Mediated Reactions: Testing
Skin Test
Skin pricked through drop of purified protein extract
Negative predictive value >95%
Positive predictive value 50%
Sensitivity >90%
Specificity 50%
Results available in minutes
Less expensive than laboratory testing ($16 for SPT vs. $33 for RAST)
Blood test
RAST test: CAP-RAST now able to give quantitative result
Not as sensitive as SPT for foods for which we do not know cutoff values
Can do if patient on antihistamines or if skin not clear
Can be used to follow levels and predict likelihood of patient passing an oral challenge

24. Skin Testing
A negative test strongly indicates against that food being responsible for the allergic reaction
A positive test usually requires correlation with a clear positive history or with a food challenge
A correct result sometimes relies on the use of fresh foods
Children less than 1 year of age may have IgE mediated food allergy in the absence of positive skin tests, children less than 2 may have smaller wheals
Postiive test produces a wheal within minutes that is 3 mm or larger than the control- discussion in allergy world if size of wheal can be used as predictor for oral tolerance development of selected foods

25. Beware
Negative igE serum testing does not necessarily rule out allergy
If highly suspicious, skin or oral food challenge should be considered

26. Predictive value of IgE testing in positive or negative OFC results
Food >95% Positive ∼50% Negative
sIgE SPT sIgE SPT wheal (mm)
Egg white ≥7
≥2 if age <2 y ≥7 ≤2 ≤3
Cow's milk ≥15
≥5 if age <1 y ≥8 ≤2
Peanut ≥14 ≥8 ≤2 = history of prior reaction
≤5 = no history of prior reaction ≤3
Fish ≥20
Choose testing wisely – not at random for multiple things

27. Double-Blind, Placebo-Controlled Food Challenge
Considered the “gold standard “ for diagnosing food allergies
Selection of foods is based on history and/or diagnostic tests
A positive skin test to a food to which a patient reported an anaphylactic reaction may be considered diagnostic and DBPCFC unecessary
Oral food challenges have potential of decreasing anxiety for kids and families r/t anaphylaxis – giving kids more normal lives – also has postiive nutritional implications – particularly milk –adding needed calcium and vit d to diet
OFC – ALWAYS IN OFFICE

28. IgE Mediated Reactions: Oral Challenge Testing
Oral food challenge is the gold standard for diagnosis
DBPC is ideal, but not often done outside of academic/research setting
Open food challenge is most common
Start with very small dose and slowly increase to normal serving size
Must have emergency medicine available
Results can be confounded by subjective reactions
Reevaluation of children with food allergies is warranted to determine if still with allergy – periodic every 1-2 years

29. The Oral Allergy Syndrome
Symptoms are associated with the ingestion of fresh fruits and vegetables
Symptoms generally have a rapid onset and resolution
Characteristic symptoms include pruritus of the lips, palate, tongue and throat.
Confined to the oropharynx

30. The Oral Allergy Syndrome
Symptoms of throat closing are a potential systemic and life-threatening reaction and should not be confused with symptoms of oral allergy syndrome, which is a self-limiting condition
Oral allergy syndrome is frequently seen in patients with seasonal allergic rhinitis due to cross-reactivity between some pollens and foods.
Oral allergy syndrome or OAS is a type of food allergy classified by a cluster of allergic reactions in the mouth in response to eating certain (usually fresh) fruits, nuts, and vegetables that typically develops in adult hay fever sufferers.[1]
OAS is perhaps the most common food-related allergy in adults. OAS is not a separate food allergy, but rather represents cross-reactivity between distant remnants of tree or weed pollen still found in certain fruits and vegetables. Therefore, OAS is typically only seen in tree and weed allergic patients, and is usually limited to ingestion of only uncooked fruits or vegetables.[2]
Another term used for this syndrome is '"Pollen-Food Allergy."' In adults up to 60% of all food allergic reactions are due to cross-reactions between foods and inhalative allergens.[3]
OAS is a Type 1 or IgE-mediated immune response, which is sometimes called a "true allergy". The body's immune system produces IgE antibodies against pollen; in OAS, these antibodies also bind to (or cross-react with) other structurally similar proteins found in botanically related plants.
OAS can occur anytime of the year but is most prevalent during the pollen season. Individuals with OAS usually develop symptoms within a few minutes after eating the food.[4]

31. Pollens and cross reactive foods in patients with OAS
Pollen/plant Fruit/vegetable
Birch Apple, cherry, apricot, carrot, potato, kiwi, hazelnut, celery, pear, peanut, soybean
Ragweed Melon (eg, cantaloupe or honeydew), banana
Grass Kiwi, tomato, watermelon, potato
Mugwort Celery, fennel, carrot, parsley
Latex Banana, avocado, chestnut, kiwi, fig, apple, cherry

32. Food is the leading cause of anaphylaxis in children

33. Anaphylaxis in Food Allergy: Definition
Criterion 1 — Acute onset of an illness (over minutes to several hours) involving the skin, mucosal tissue, or both AND AT LEAST ONE OF THE FOLLOWING:
Respiratory compromise (eg.,dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (eg.,hypotonia, syncope, incontinence).
Criterion 2 — TWO OR MORE OF THE FOLLOWING that occur rapidly after exposure TO A LIKELY ALLERGEN FOR THAT PATIENT (minutes to several hours):
Involvement of the skin-mucosal tissue
Respiratory compromise
Reduced BP or associated symptoms
Persistent gastrointestinal symptoms
Criterion 3 — Reduced BP after exposure TO A KNOWN ALLERGEN FOR THAT PATIENT (minutes to several hours).

34. Anaphylaxis in Food Allergy: Epidemiology
Food allergy is estimated to cause 50% of anaphylaxis cases treated in EDs
One survey estimated 30,000 ED visits per year due to food-induced anaphylaxis
Peanuts, tree nuts and seafood are responsible for most cases in adults
Milk and egg cause most cases in children
Estimated 150 deaths per year from food allergy in U.S.

35. Non-IgE-mediated Food Hypersensitivity

36. IgE vs. IgG testing
IgG antibodies are found in both allergic and non-allergic people. Experts believe that the production of IgG antibodies is a normal response to eating food and that this test is not helpful in diagnosing a food allergy.
At present, there are no reliable and validated clinical tests for the diagnosis of food intolerance. While intolerances are non-immune by definition, IgG testing is actively promoted for diagnosis, and to guide management. These tests lack both a sound scientific rationale and evidence of effectiveness. The lack of correlation between results and actual symptoms, and the risks resulting from unnecessary food avoidance, escalate the potential for harm from this test. Further, there is no published clinical evidence to support the use of IgG tests to determine the need for vitamins or supplements. In light of the lack of clinical relevance, and the potential for harm resulting from their use, allergy and immunology organizations worldwide advise against the use of IgG testing for food intolerance.

37. Food induced enterocolitis
Generally presents in infants between 1 week and 3 months of age
Major symptoms are protracted vomiting and/or diarrhea
Cow milk, soy protein or both are most often responsible
Symptoms usually resolve after 72hours of allergen avoidance
Whey based formula as a place to start for babies with family hx of allergies –
Formulas to start with are hydrolyzed casein based formulas then to amino acid based formulas

38. Food-induced proctocolitis
Presents during first few months of life
Hematochezia is (gross or occult) is a distinguishing feature
Cow milk or soy protein are usually implicated
May co-exist with Clostridium Difficile infection
The c-diff is after 8 weeks – guiac positive mucousy stools +/- vomiting

39. Food-induced Enteropathy
Malabsorption syndrome
Presents in first several months of life
Cow’s milk sensitivity is most frequent cause
Symptoms :
Protracted and/or greasy diarrhea
Vomiting
Failure to thrive
Intestinal lesions may require 6 to 18 months allergen avoidance for complete resolution

40. The conundrum of formulas
Milk based
Soy based
Hypoallergenic formulas
Amino acid based formulas
The nursing mom

41. Allergic Eosinophilic Gastroenteritis/Esophagitis
Intolerance to multiple foods, IgE or non-IgE mediated mechanisms
Eosinophils infiltrate esophageal, gastric or intestinal walls
Symptoms include nausea/ vomiting, abdominal pain, diarrhea, GERD, early satiety or food refusal, dysphagia, weight loss, growth failure
Symptoms subside within 3-6 weeks of allergen elimination
- this is diagnosed endoscopically – have greater than 20 eos per hpf – treatments of allergic disease are 1-2 things – eoe – pulmicort vs diet vs amino acid diet
Gastritis – use mast cell stabilizers – gastrocrom

42. Elimination Diets Therapeutic trials
Used only for a limited period of time (10-14 days)
Monitor outcomes closely
Adequate education before starting is key to avoiding failure

43. Elimination Diets Basic Elimination Diet (6 food)
Milk, soy, egg, wheat, tree nut, peanut, fish/shellfish
Targeted Elimination Diet
Severe Elimination Diet

44. Celiac Disease
Gluten-sensitive celiac disease produces a more extensive enteropathy, leading to malabsorption
Sensitivity is to gliadin, the alcohol-soluble portion of gluten
Found in wheat, oat, rye and barley
Treatment requires lifelong elimination of gluten
This is an iga mediated response – not an allergy – it is not an allergy to wheat -

45. Food Intolerance Accounts for the majority of adverse food reactions
Not an immunologically mediated response
May include:
Abnormal metabolic responses (ie lactase deficiency)
Unusual susceptibility to pharmacologic substances in certain foods (ie caffeine, tyramine)

46. Fig E1
Journal of Allergy and Clinical Immunology  , e43DOI: ( /j.jaci )
Copyright © Terms and Conditions

47. Managing the Patient with Food Allergy
Nonpharmacologic Management:
Strict avoidance of the offending food allergens is the only proven therapy
Symptomatic reactivity to food allergens is often lost over time except for:
Peanuts
Fish
Tree nuts
Shellfish
Ensure families understand what needs to be removed and that unnecessary food removal do not occur – ie if allergic to wheat – ensure not all grains removed –just cause
Extensive eliminiation diets are not warranted
This is different in tree and peanut situations – more targeted testing may need to be conducted same with shellfish –
In milk – goats and sheep milk should also be avoided as are casein based

48. Managing the Patient with Food Allergy
Pharmacologic Management
Epinephrine is the treatment of choice for severe reactions to food
Doses may be repeated every 15 minutes for up to 3 doses
Delayed, biphasic or prolonged anaphylaxis occurs in more than 20% of cases and so extended observation is required in all cases
Prophylactic management has not been proven safe or effective

49. Patient Education
Allergen identification (i.e., how to read food labels)
Avoidance strategies and counseling
Symptom recognition
Cautions regarding the possibility of a life-threatening reaction
What to do in case of accidental ingestion
Development of a treatment plan
How to self-administer epinephrine
New data from the allergy world is stuggesting that regular exposure to heat modified egg and milk protein in allergic patients may be tolerated in up to 70% of patients and may be clinically beneficial –
Recent data suggests that it accelerates development of tolerance – an observed food challenge with something like a muffin may be warranted in a controlled environement to ensure safe consumption

50. Other concerns Nutrition Bullying Social stigma Siblings
Food introductions in infants
Vit d
Consider testing siblings of kids with high allergies – consider testing prior to introduction particularly peanuts, egg and milk – in babies with milk and egg allerries – 69% had sensitization to peanuts – should be done by allergist –
Experts recommend that intro of solid foods potentially allergenic foods should not be delayed more than 4-6 months of age – recommendation is based on recent studies that support delayed introduction of allergens such as milk egg wheat and peanuts as possible risk factors for allergy or atopic disease

51. Food Allergy: Prevention
We do not know how to prevent food allergies
Diet restriction in pregnancy not recommended
Exclusive BF for 6 months is best
Diet restriction while BF: in high risk patients, avoid high risk foods (peanuts, tree nuts, milk, egg)
If supplementing, extensively or partially hydrolyzed formula is best
No evidence that delaying introduction of solid foods has any effect

52. Food Allergy: Resources for Patients
Food Allergy and Anaphylaxis Network
American Academy of Allergy, Asthma, and Immunology
American College of Allergy, Asthma, and Immunology