A simple case of cow’s milk allergy?€¦ · product label even if it is only a minor ingredient...

A simple case of cow’s milk allergy?

Carina Venter PhD RD Brian P Vickery MD

Disclosure Brian Vickery

• Employment: Pediatric Institute of Emory University + Children’s Healthcare of Atlanta

• Consultant/Advisor: Aimmune Therapeutics; AllerGenis, LLC; Food Allergy Research and Education (FARE); Reacta Biosciences

• Grant support: NIH-NIAID; FARE; Genentech • Clinical investigator: Aimmune; DBV Technologies; Regeneron • Equity interests/stock ownership: none

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Disclosure Carina Venter

• Provided and reviewed education material for: • Danone • Abbott • Reckitt Benckiser Group • DBV technologies • Research support • Reckitt Benckiser Group

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Objectives

• Describe the process involved in the diagnosis the different presentations of cow’s milk allergy in early childhood

• Develop increased knowledge on formula choice and dietary management of cow’s milk allergy

• Be able to advise parents on suitable treatment options for tolerance development

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Different presentations of cow’s milk allergy Cow’s milk

allergies

IgE mediated cows milk allergies

Non-IgE mediated cow’s milk allergies

Food Protein induced enterocolitis

Other forms of non-IgE mediated cow’s milk allergies

Eosinophilic Esophagitis

Mild to moderate non-IgE mediate cow’s milk llergy

Cow’s milk allergy is the most complex presentation of food allergy in early childhood

Trevor Brown

Different presentations of cow’s milk allergy Cow’s milk

allergies

IgE mediated cows milk allergies

Non-IgE mediated cow’s milk allergies

Food Protein induced enterocolitis

Other forms of non-IgE mediated cow’s milk allergies

Eosinophilic Esophagitis

Mild to moderate non-IgE mediate cow’s milk llergy

Dietary management

Diagnosis • History • Testing if applicable • Food elimination followed by

Food reintroduction/trial or “challenge” phase

Management phase

IgE mediated cow’s milk allergies

History • Dietary focused allergy history • Symptoms within 2 hours of

consumption • Foods 14 major allergens

Skypala et al. Clin Exp Allergy 2015

Children’s Healthcare of Atlanta | Emory University

Food Allergy Evaluation: History Is Critical; Ask Specific Questions

• Suspected culprit food protein (i.e., egg vs. red Gatorade): – Which was it? One of the “big 8?” – What form did they eat? Had they eaten it before? – How much? – Have they eaten it again - ask about other forms - since the episode?

• What happened then? – Timing & sequence of symptoms?

• Yes: Hives, swelling, abd pain, vomiting, wheezing/coughing, significant AD flare, anaphylaxis within 15 – 60 (up to 120) min

• No: headaches, fatigue, flat nonpruritic red rash on face or bottom; significant delay between exposure & sx

– Did the episode require treatment?

Children’s Healthcare of Atlanta | Emory University

What about a young child who has never eaten the food?

What if the patient has atopic dermatitis?

Children’s Healthcare of Atlanta | Emory University

Decision Points

Sampson HA Allergy 2005 (60): 19-24

*** These numbers predict likelihood of symptoms, not severity, and were studied in patients with a high pretest probability of disease ***

Note: not Class IV

Children’s Healthcare of Atlanta | Emory University

Diagnostic Limitations

• Most direct-to-consumer testing is worthless • Conventional tests are often misinterpreted • Correctly interpreted tests still have significant limitations:

– probabilistic, not diagnostic – cannot determine alone if patient is allergic or tolerant – cannot determine how much food it might take to react – cannot tell “severity” / offer assessment risk

• Every patient is thus assumed to be at high risk for a life-threatening reaction – Important downstream effects for families, communities, schools, etc.

Chafen JJ et al JAMA 2010

Children’s Healthcare of Atlanta | Emory University

Key Diagnostic Points

1. Skin & blood tests are only markers of exposure, not disease (TB) 2. A convincing history of symptoms after ingestion is key

– If the child can eat the food sometimes, allergy is not likely

3. If a prick skin test, done correctly, is negative, allergy is not likely – NPV > 90%

4. In general, strongly positive tests might be helpful – Prick test > 8-10 mm or IgE level above “decision point”

5. Indeterminate test results are common and can be confusing, especially in certain settings (e.g., AD, no/poor history)

6. If uncertain, the gold standard for diagnosis is oral challenge

Case 1

• Case scenario: Emily • You are seeing a 6-month old girl who had an infant cereal containing

milk, which her day care attendant gave to her • She developed wide-spread urticaria, breathing difficulties,

angioedema and was rushed to the ER (A&E). • Mother still breast feeding, has not given Emily any milk containing

food, but mother has been consuming milk containing food while breast feeding and Emily has not had any problems

History

• Breast fed with maternal consumption of cow’s milk: Ice cream, yogurt, cheese, cake, cookies, butter

• Not tried infant formula • Eaten some fruit and

vegetable purees • Eaten baby rice • Not tried yogurt • Infant cereal:

SPT results as follow:

• Histamine 4 mm

• Saline 0 mm

• Milk 8 mm

Do you think she has a cow’s milk allergy?

• Yes • No • Need further testing: Specific IgE tests • Need further testing: component resolved diagnostic testing

Allergy testing should only be carried out if there is clinical suspicion of cow's milk allergy as it has poor predictive value as a screening tool. Luyt et al. Clin Exp Allergy 2014

Specific IgE results

• Milk specific IgE 12 kuA/L • Milk specific casein 10 kuA/L • Milk specific beta-lactaglobulin 6 kUA/L

Mukkada 2010; Furuta 2018 18

Are you going to perform a food challenge?

• No • Yes to cow’s milk • Yes to baked milk

Can babies react to cow’s milk allergens via breastmilk? 1. No

2. Yes

3. Depends on the type of cow’s milk allergy

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Symptoms while breastfeeding

Rationale and substantiation: • Host et al. 1988:

• Only 1 prospective study • 0.5% presented while on breast milk only (out of 2.2%)

• Some infants with CMA can react to residual β-lactoglobulin transferring to breast milk Breast milk: 0.9-150ug/l (median 4.2ug/l) EHFs: 0.84 -14.5ug/l

• However limited evidence available to substantiate this as first line formula if breast milk not available

Breast milk is the preferred nutrition for infants with CMA - Infant should continue taking breast milk while, if advised, mom avoids dairy under medical supervision

1. Host, et al. Acta Paediatr Scand. 1988;77:663-70. 2. Host, et al. Allergy. 2004; 59: 45–52. 3. Makinen-Kiljunen, et al. Clin Exp Allergy. 1993;23:287–91. 4. Rosendal, et al. J Dairy Sci. 2000;83:2200–10. 5. Meyer, et al. J Allergy Clin Immunol Pract. 2018;6:383-99. 6. Koletzko, et al. J Pediatr Gastroenterol Nutr. 2012;55:221-9. 7. Ludman, et al. BMJ. 2013;347:f5424. 8. Venter, et al. Clin Transl Allergy. 2013;3:23.

The spectrum of cow’s milk based formulas

1. https://www.seas.upenn.edu/~cis535/Fall2004/HW/GCB535HW6b.pdf. July 3, 2018. 2. American Academy of Pediatrics Committee on Nutrition. Pediatrics. 2000;106:346-9. 3. Lowe, et al. Expert Rev Clin Immunol. 2013;9:31-41. 4. Hongsprabhas, et al. Joint ACS AGFD-ACS ICSCT Symposium; 2014.

Formula type: Amino acid- based (AAF)

Extensively hydrolyzed

(eHF)

Partially hydrolyzed Regular (Intact protein)

Protein source

100% free amino acids

Cow milk Cow milk Cow milk

Peptide size, kilodaltons

N/A (free AAs ~0.121)

Most <1.52

Up to 5% >3.53

Dairy: Most <53 Dairy: 14-673

Soy: 20-2254

Presentation or condition

NIAID US guidelines

DRACMA international guidelines

ESPGHAN European guidelines

BSACI guidelines

Breast-feeding with ongoing symptoms (already on maternal elimination diet) or requiring formula, e.g. to supplement

EHF or AAF “Prior to initiating an oral food challenge… until the allergic [sic]

food is identified”

Not specified EHF or AAF

“In breast-fed infants with severe symptoms …it is common

practice in many countries to use AAF for diagnostic elimination...”

AAF if symptoms when

exclusively breastfed

Symptoms while breastfeeding

Limited data suggest an AAF can be used first line if formula is needed to supplement or replace breast milk because intolerance to eHF may occur

First choices for CMA and related conditions ONLY when formula is needed

1. Meyer, et al. J Allergy Clin Immunol Pract. 2018;6:383-99. 2. Boyce, et al. Nutr Res. 2011;31:61-75. 3. Koletzko, et al. J Pediatr Gastroenterol Nutr. 2012;55:221-9. 4. Luyt, et al. Clin Exp Allergy. 2014;44. 5. Ludman, et al. BMJ. 2013;347:f5424. 6. Venter, et al. Clin Transl Allergy. 2013;3:23. 7. Fiocchi, et al. Pediatr Allergy Immunol. 2010;21 Suppl 21:1-125. Hill, et al. Clin Exp Allergy. 2007;37:808-22. 8. de Boissieu, et al. J Pediatr. 1997;131:744-7. 9. Host, et al. Allergy. 2004;59 Suppl 78:45-52.

Other information

• Label reading

• Foods to avoid

• Substitute foods

• Weaning advice: Flavor, texture, variety

• Nutritional adequacy of diet

Label Reading Food Allergen Labeling Consumer Protection Act (FALCPA)

• Milk • Egg • Wheat • Soy • Peanut • Tree nut* • Fish* • Crustacean shellfish* *Specific species must be listed

Incidental Ingredients

• A “major food allergen” may not be omitted from the

product label even if it is only a minor ingredient

• Allergens not considered “major” may remain unidentified on product labels

Front of package labeling not useful

• “Dairy free” no definition • “Non-dairy” defined but allows casein • MUST READ ingredient list and contains statement

https://farrp.unl.edu/resources/gi-fas/opinion-and-summaries/dairy-free-and-non-dairy

Allergens can be listed in the ingredient list

Allergens can be listed in the “contains” statement

Flour (wheat), sugar, milk, egg, natural flavor (soy)

Flour, sugar, milk, egg, natural flavor Contains: wheat, milk, egg, soy

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Cross contact

• Precautionary Allergen labeling (PAL) • May contain… • Manufactured in a facility… • Manufactured on shared equipment…

VOLUNTARY AND UNREGULATED

IF it is NOT there does not mean it is definitely safe/not contaminated

Remington BC, et al. Food and chemical toxicology. 2013

Ford et al. 2010

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Who should avoid

products with PAL?

• Patients with FPIES? • Not typically

• Patients with EoE?

• Maybe

• Patients tolerating baked milk or baked egg? • Depends on the product

• Patients with high threshold?

• Not easy to define

FALCPA Exempts

• Foods that are placed in a wrapper or container or prepared on a made-to-order basis

• FALCPA does not cover foods “served in restaurants or other establishments in which food is served for immediate human consumption”.

• Alcoholic beverages, medications, anything regulated by the USDA (fresh meat, poultry, eggs fruits and vegetables).

FALCPA exemptions

• Are there any other areas not covered by FALCPA?

• Yes, there are quite a few areas where the law does not apply:

• · Prescription drugs • · Over-the-counter drugs • · Personal care items such as cosmetics, shampoo, mouthwash, toothpaste or

shaving cream. • · Any food product regulated by the USDA, which includes meat, poultry, or

certain egg products. • · Any product regulated by the Alcohol, Tobacco Tax and Trade Bureau (ATTB).

This includes alcoholic drinks, spirits, beer and tobacco products. • · Any restaurant foods or foods that are placed in a wrapper or container in

response to a person's order for that food. This includes street vendors, festival foods, fast food restaurants.

• · Kosher labeling • · Pet: foods, supplements, and supplies

• • More information on FALCPA: https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/Allergens/ucm106890.htm •

Milk Oral Immunotherapy – 5 RCTs

Taniuchi et al Hum Vaccin Immunother 2017

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Nowak-Wegrzyn. JACI In Pract. 2018

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Nowak-Wegrzyn. JACI In Pract. 2018

If baked milk tolerant: How much baked milk • Know exactly how much milk the patient has tolerated • THEN you can provide specific guidance For instance published recipes provide • No more than 1/6th cup of milk per serving (1.3 g protein)

• For example: I cup of milk in a recipe that yields 6 servings

Leonard, Caubet, Kim, Groetch, Nowak-Wegrzyn. JACI In Pract. 2015

Caution: Read Product labels carefully

1. Rule: Milk or egg ingredient is the 3rd ingredient or further down the list of ingredients. Although there is no way to critically evaluate this practice, it has been used effectively.

2. Final cooking time will depend on the size of the finished product- most published reports suggest 30 min for 350 degrees

3. All baked products must be baked throughout and not wet or soggy in the middle.

Leonard et al. 2015

Non-IgE mediated cow’s milk allergy

Food protein induced enterocolitis syndrome

History

• The NIAID Food Allergy Guidelines recommend using the medical history and OFC to establish a diagnosis of FPIES

• When history indicates that infants or children have experienced hypotensive episodes or multiple reactions to the same food, a diagnosis may be based on a convincing history and absence of symptoms when the causative food is eliminated from the diet.

• Boyce et al. Journal Allergy Clin Immunology 2010 • Nowak-Wegrzyn et al. Journal Allergy Clin Immunology 2017

Skin prick tests/Specific

IgE tests

• Food-specific IgE and skin prick testing may be performed to provide complete evaluation for food sensitization, particularly when considering a food challenge.

• Consider food-specific IgE and skin prick testing in children with FPIES as a positive test can infer a greater chance of persistent disease.

• Boyce et al. Journal Allergy Clin Immunology 2010 • Nowak-Wegrzyn et al. Journal Allergy Clin Immunology 2017

Case 2: Jennifer

• Breastfed infant just starting solid foods

• At 5 months of age, had first episode of repetitive, non-bloody, non-bilious vomiting followed by diarrhea and lethargy after 4th day of rice cereal mixed with cow’s milk formula

• Mother suspected GI illness and treated with rehydration fluids and Jennifer improved

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Jennifer

• Two days later, rice cereal was offered again (mixed with cow’s milk formula) with a recurrence of symptoms 2 hours later

• This time they went to the emergency department and intravenous fluids were given and mom tells the doctor that she suspects the rice cereal

• They were referred to the allergy clinic

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Jennifer – Diagnosis

History - Currently eating apple, banana - Quinoa, baby rice

- Reaction: Baby rice WITH standard

infant formula on 2 occasions

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Perform any testing?

• Yes (required to diagnose FPIES)

• No – never

• Yes (to investigate co-morbid sensitization)

Perform a food challenge?

• Yes • No • Yes – to baked milk

When do you challenge for FPIES?

• OFC every 18-24 months in patients who have not had a recent reaction.

• Protracted vomiting and dehydration necessitate fluid resuscitation in approximately 50% of reactive challenges.

• Considered high-risk and should be conduction in a setting with IV access.

• May consider challenge to high-risk foods never ingested in the office

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• Jarvinen et al. Journal of All Clin Immunol in practice. 2013 • Nowak-Wegrzyn et al.. Journal of All Clin Immunol 2009.

Maternal avoidance of cow’s milk?

Mukkada 2010; Furuta 2018 50

YES NO

1

Formula choice – ONLY IF NEEDED

Meyer, et al. 2018; Fiocchi, et al. 2010; Koletzko, et al. 2012; Luyt, et al. 2014; . Boyce, et al. 2011

Clinical presentation DRACMA BSACI Guidelines NIAID US Guidelines ESPGHAN

Anaphylaxis AAF AAF No specific recommendation AAF

Acute urticaria or angioedema EHF EHF No specific recommendation EHF

Atopic eczema/dermatitis EHF EHF No specific recommendation EHF

Eosinophilic Esophagitis AAF AAF

The NIAID guidelines acknowledge that trials in EoE have shown symptom relief and endoscopic improvement in almost all children on AAF/elemental diet, though no specific recommendation on formula choice is made.

AAF (as specified by current ESPGHAN guidelines on EoE)

Gastroesophageal reflux disease EHF EHF No specific recommendation EHF

Cow’s milk protein-induced enteropathy EHF EHF unless severe in which case AAF No specific recommendation EHF but AAF if complicated by faltering growth

FPIES EHF AAF Hypoallergenic formulas are recommended.

EHF

Proctocolitis EHF EHF No specific recommendation EHF

Breast feeding with ongoing symptoms (already on maternal elimination diet) or requiring a top-up‡ formula

No recommendation AAF

No specific recommendation With severe symptoms that are complicated by growth faltering a

hypoallergenic formula up to 2 weeks may be warranted. In many

countries, AAF is used for diagnostic elimination in extremely sick

exclusively breast-fed infants. Although this is not evidence based,

it is aimed at stabilizing symptoms.

Indications that a child is more likely to require and amino acid based formula

symptoms not fully resolved on EHF

faltering growth/failure to thrive

multiple food eliminations

severe complex gastrointestinal food allergies

eosinophilic esophagitis

severe eczema

53 Meyer et al. 2017

Structured Visits

• Burden awareness is key

• Assess QOL, history and trajectory- utilize ancillary staff

• Discuss previous recommendations: “What has and what has not worked?”

• Ask questions: “Are you having a difficult time feeding your child?”

• Lifestyle competency

• Evaluate short and long term goals

• Informed decision: Educate and provide options

• Division of responsibility

• Assess readiness and make appropriate referrals for practical management obstacles

• Utilize available resources: www.fpies.org, Guideline Pocket Guide

• Slide courtesy of Fallon Matney, IFPIES.org

Co-existing food allergies

Nowak-Wegrzyn et al. 2016 55

FPIES foods and their importance in the diet Food Nutrients

Grains Carbohydrate, fiber, thiamine, riboflavin, niacin, calcium, iron, folate, calcium, phosphorous, potassium, pantothenic acid

Poultry Protein, fat, selenium, phosphorous, potassium, zinc, Iron, vitamin B6, Niacin, B12

Legumes Folic acid, Pantothenic acid, Niacin, Thiamine, Pyridoxine, Ascorbic Acid, Vitamin K, Vitamin A, Calcium, Iron, Copper, Zinc and Manganese

Sweet potato

Vitamin A, Pantothenic acid, thiamin, niacin, riboflavin, magnesium, manganese, and potassium

Milk Protein, carbohydrate, fat, vitamin A, vitamin D, riboflavin, pantothenic acid, vitamin B12, calcium, magnesium, phosphate

Soy Protein, Thiamine, riboflavin, pyridoxine, folate, calcium, phosphorus, magnesium, iron, zinc, protein, fiber

Egg Protein, Riboflavin, biotin, protein, vitamin A, vitamin B12, vitamin D, vitamin E, pantothenic acid, selenium, iodine, folate

Venter and Groetch 2014; Raquel Durban

Nutritional considerations

What I do?

• Provide guidance during the introduction of complementary foods – give a list of foods

• Monitor growth (weight and height/length)

• No need to avoid products with precautionary allergen labeling in patients with FPIES

• Textures and chewing: Recommend foods that prevent all levels of feeding dysfunction

Comparison of Cow’s Milk (CM) substitutes- many do not provide adequate nutrition (low protein and fat). Choose carefully and consider patient age!

Cow milk or enriched substitute

KCAL/ 8 oz

Protein g Fat g Calcium mg/ Vitamin D IU

Cow’s Milk 150 8 8 350/100

Soy 100 7 4 300-450/100

Pea Protein 100 8 4.5 450/120

Oat 120 4 3 300/100

Rice 120 1 2.5 300/100

Coconut 80 0 4.5 100-450/100

Almond 50 1 2.5 300-450/100 58

Choose calcium and vitamin D

fortified!

Slide: Marion Groetch 59

Lower risk Moderate risk Higher risk Vegetables

Broccoli, cauliflower, parsnip, turnip, pumpkin

Squash, carrot, white potato, green bean (legume)

Sweet potato, green pea (legume)

Fruits Blueberries, strawberries, plum, watermelon, peach

Apple, pear, orange Banana

High iron foods Lamb, fortified quinoa cereal, millet

Beef, fortified grits and corn cereal, wheat (whole wheat and fortified), fortified barley cereal

Fortified, infant rice and oat cereals.

Other Tree nuts and seed butters* (sesame, sunflower, etc.) *Thinned with water or infant puree to prevent choking

Peanut, other legumes (other than green pea)

Milk, soy, poultry, egg, fish

Mild to moderate Non-IgE mediated cow’s milk allergy

Fox et al. Clin Translation Allergy 2019

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IMAP guidelines

Fox et al. 2019

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Case 4

• 3 month old infant

• Reflux does not resolve on thickening milk

• Eczema not responding to topical treatment

• No-one sleeps

History

• https://www.allergyuk.org/health-professionals/mapguideline

Fox et al. 2019

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TESTING

How will cow’s milk be introduced upon symptom resolution? 1. If breast feed – just reintroduce all milk containing food back into

diet 2. If formula feeding – carefully increase formula milk intake 3. Do the milk ladder 4. 1 and 2

Reintroduction of Cow’s Milk to Confirm Diagnosis

https://www.allergyuk.org/health-professionals/mapguideline

After 6 – 9 months of milk avoidance, how will cow’s milk be introduced into the diet? 1. If breast feed – just reintroduce all milk containing food back into

diet 2. If formula feeding – carefully increase formula milk intake 3. Do the milk ladder 4. 1 and 2

Changes to the Milk Ladder

Eosinophilic Esophagitis I DON’T THINK WE NEED TO DO EOE – I AM DOING THE EOE TALK THE DAY BEFORE

Eve is a 28-month-old female with EoE • Medical history: EoE on diet therapy excluding milk (empiric) and

eggs, peanut, almond and barley (test directed). • Dietary history: Parents are concerned because Eve eats a very

small volume of food. • Supplements: Poly Vi Fluor (400 IU D), • L'il Critter gummies calcium and D (200 mg calcium and 200 IU

vitamin D) • L'il Critters Vitamin C (126 mg vitamin C and 200 IU D and 3 mg zinc)

with Echinacea.

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Growth

• Growth history: Growth from birth has been following closely around the 25th percentile.

• She has recently had a weight loss of 1.4 pounds (from 23-24 months of age) and there has been no follow up weight check since this time. Weight now dropped to the 3rd percentile.

• Eve was not present so weight/height could not be documented. Mukkada 2010; Furuta 2018 72

Food intake Foods currently in diet: • Meat: Chicken, turkey, beef and pork • Vegetable: Carrot, cucumber, lettuce, olive, onion, squash, tomato

and white potato • Fruit: Apple, banana, cantaloupe, grape, lemon, mango, orange,

pear, pineapple, raspberry and watermelon • Grain: Wheat, rice, corn, oat (Apple Jacks Cereal) • Other: Soy, cod fish

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Snacks

• Snack-food is provided on demand; parents report Eve is constantly asking for foods (as she is hungry)

• Few actual meals - mostly salty (pretzels, veggie sticks) and sweet snacks (crackers, sweetened dry cereal snacks, fruit snacks, fruit, fruit punch) and an occasional slice of bologna or chicken nugget or 1/4 hotdog

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Should we add a commercial milk/beverage or formula?

1. No need; use commercial milks 2. Extensively hydrolyzed formula 3. Amino acid based formula

Mukkada 2010; Furuta 2018 75

Growth and EoE – mainly elemental formulas

76

Study Growth outcome

Kelly et al. 1995 ‘…poor weight gain had resolved’

Al-Hussaini et al. 2013 Corrected growth after 2 months of therapy

Liacouras et al. 2005 ‘…no significant weight loss’, ‘or alteration of growth parameters (height, weight, head circumference)’ in those on dietary therapy, however reported that n=5 patients considered to have failure to thrive had a significant increase in weight after receiving AAF

Kagalwalla et al. 2005 Children with failure to thrive on AAF (n=14) mean weight gain was 1.03kg (range 0.1-2.1kg), and of children identified with failure to thrive on the EED (n=5), mean weight gain was 1.32kg (range 0.9-2kg), after six weeks of intervention

Colson et al. 2014 (n=59) diet height and weight gains were significant after 5 months, but weight-for-height z-scores did not change.

Atwal et a. 2019

Extensively hydrolyzed formula vs. Amino acid based formula

Mukkada 2010; Furuta 2018 77

Comparison of Cow’s Milk (CM) substitutes- many do not provide adequate nutrition (low protein and fat). Choose carefully and consider patient age!

Cow milk or enriched substitute

KCAL/ 8 oz

Protein g Fat g Calcium mg/ Vitamin D IU

Cow’s Milk 150 8 8 350/100

Soy 100 7 4 300-450/100

Pea Protein 100 8 4.5 450/120

Oat 120 4 3 300/100

Rice 120 1 2.5 300/100

Coconut 80 0 4.5 100-450/100

Almond 50 1 2.5 300-450/100 78

Choose calcium and vitamin D

fortified!

Should we add a formula?

1. No need; use commercial milks 2. Extensively hydrolyzed formula 3. Amino acid based formula

Mukkada 2010; Furuta 2018 79

Follow-up

• The follow up endoscopy was improved but Eve still has some occasionally regurgitation/vomiting and she had 34 eos/hpf in the proximal esophagus.

• The family opted for further dietary restriction and wheat and soy were also removed.

80

What to advise parents about “precautionary advisory labelling? 1. Exclude these foods from her diet 1. These foods can be allowed

Mukkada 2010; Furuta 2018 81

82

Avoiding precautionary advisory labelling?

Cianferoni et al. 2019

Molina-Infante 2017 Spain Adults

Molina-Infante 2014 Spain Adults Lucendo 2012 Kagalwalla 2017

USA Pediatric CEGIR study 2019

Milk All dairy products (either goat’s or sheep’s milk can cross-react with cow’s milk) Mammalian milk Milk Milk Milk

Egg Egg Egg Egg Egg Egg

Wheat All gluten-containing grains (cross-reactive with wheat, including barley, rye, and oats)

Wheat/gluten-containing grains Cereals (wheat, rice, corn) Wheat Wheat

Soy Legumes, including soy, lentils, chickpeas, peas, beans, and peanuts

Soy/legumes Legumes/peanuts, and soy Soy Soy

Nuts All kind of nuts NA Nuts NA NA

Seafood Fish and seafood NA Fish/seafood NA NA

Other allergens?

Food allergens known to cause oral allergy syndrome symptoms were avoided already by patients before enrollment

No mention No mention No mention NA

May contain

Patients were also advised to avoid processed foods because of the high likelihood of containing wheat or milk traces, including processed meats (eg, sausages and hamburgers), soups, sauces, pizza, mashed potato, and instant rice

No mention No mention No mention NA

Discussion points

What recommendations would you make to help Eve’s parents manage this elimination diet? What recommendations would you make regarding follow-up endoscopy? Would you try more foods? How often?

Mukkada 2010; Furuta 2018 83

84

Food Group Daily Servings Suggested Foods Grains (no wheat)

Select breads, cereals, pastas, crackers, and baked goods made with allowable grains/grain substitutes: Amaranth; arrowroot; barley; black, white, fava, and garbanzo beans; buckwheat; corn; millet; oats (gluten-free); potato (white or sweet); quinoa; rice; rye; tapioca Gluten-free foods are typically wheat-free. Verify foods are also soy, milk, nut, and egg-free.

Protein Foods (no eggs, fish, nuts)

Eat a variety of protein foods (no eggs, fish/shellfish, or peanuts/tree nuts) each week. Select chicken/turkey, pork loin, and lean beef.

Milk Alternative† (no soy)

Coconut, hemp, or rice milk Coconut or hemp yogurts Pea protein or rice cheeses Coconut ice creams Elemental formula: Elecare® Vanilla, Neocate® Jr, Alfamino® Jr

Vegetables

Aim to eat a variety of colors daily. Include dark green, red, orange, and other vegetables (e.g., spinach, broccoli, beets, tomato, carrots, squash, sweet potato, beans (no soy), and peas) and vegetable juice.

Fruits

Aim to eat a variety of fruits daily (e.g., apples, oranges, peaches, bananas, melons, berries, pears, pineapples, plums). Choose whole fruits more often than fruit juice.

Oils

Canola, olive, safflower, sunflower, vegetable Milk and soy-free margarine Milk, soy, and egg-free salad dressings

Food reintroduction

85

1st Food • Consume for 12 weeks

EGD

• > 15 eos/hpf ⇒ FAIL ⇒ 6 week wash out • < 15 eos/hpf ⇒ PASS ⇒ Begin next food

2nd Food • Consume for 12 weeks

EGD

• > 15 eos/hpf ⇒ FAIL ⇒ 6 week wash out • < 15 eos/hpf ⇒ PASS ⇒ Begin next food

Venter, Groetch, Meyer, Netting. A patient‐specific approach to develop an exclusion diet to manage food allergy in infants and children. January 2018,

Icahn School of Medicine 2018

Thank you

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EAACI Isle of Wight Denver

Liam O’Mahony Task force on nutrition and immunomodulation

Hasan Arshad John Holloway Linda Mansflied Hongmei Zhang Wilfried Karmaus

David Fleischer Matt Greenhawt Dana Dabelea Deb Glueck Michaela Pulambo Brandy Ringham Kate Sauder Ivana Yang Lisa Testaverde