AOMA Food Allergy Talk 55 minutes[33915] · 2018. 5. 5. · Definition • IgE mediated food allergy: – An adverse health effect arising from a specific immune response that occurs

Food allergy – the old and the new Cindy Salm Bauer, MD, FAAAAIDivision of Allergy and Immunology, Phoenix Children's HospitalAssistant Professor, Dept of Medicine, Mayo Clinic Arizona

Disclosures

• None

Objectives• Define IgE mediated food allergy compared

to other adverse food reactions.• Understand the current recommendations for

preventing food allergy.• Know the benefit of food challenges,

including the use of baked food challenges.• Understand the current limitations to oral

immunotherapy and that it is not FDA-approved.

Overview• Background

– Definition– Prevalence– Natural Course– Pathophysiology

• Diagnosis • Prevention• Treatment

Definition

• IgE mediated food allergy:– An adverse health effect arising from a

specific immune response that occurs reproducibly on exposure to a given food

• Food intolerance:– A non-immune reaction, including metabolic,

toxic, pharmacologic, and undefined mechanisms

JACI 2010;126(Suppl):S1-58

Adverse Food Reactions

Immune mediated

IgE mediated

Acute urticaria/

angioedema, oral allergy syndrome,

rhinitis, asthma,

anaphylaxis, food

dependent exercise induced

anaphylaxis

Non-IgEmediated or

Cell mediated

FPIES, celiac disease, dietary protein

proctitis, allergic contact

dermatitis

Mixed

Atopic eczema, eosino-philic

gastro-intestinal disease

Non-Immune mediated

Metabolic

Lactose intolerance,

galacto-semia, EtOHintolerance

Pharmaco-logic

Caffeine, tyramine

Toxic

Scromboidor other

food poisoning

Other

Sulfites, food

aversion, anorexia, auriculo-temporal

syndrome, gustatory rhintitis

JACI 2014;133:291-307.

Prevalence

• 8 foods account for 90% of all food-allergic reactions: – cow’s milk, – eggs, – peanuts, – tree nuts– wheat, – soy, – fin fish, and – shellfish

JACI 2010;125:S116-125.

Question #1

A 14 y/o male with a history of allergic rhinitis reports suddenly being allergic to “every food” starting the first week of April. He reports that he can’t eat pears, apples, cherries, peaches, or peanuts. Bread, rice, potatoes and meat are fine as was apple pie.

Question #1

What is his diagnosis?A. Eosinophilic EsophagitisB. Oral Allergy SyndromeC.Multiple Food Allergy SyndromeD.Eosinophilic gastritis

Answer #1

B: Oral Allergy Syndrome (OAS)– “Pollen-food syndrome”– Molecular mimicry– Symptoms may worsen in season; mild– Cooked foods tend to be tolerated – Sensitization occurs via the respiratory route – Most frequent clinical manifestation of food

allergy in older children and adults

Natural Course

• Persistent into adulthood– Peanut, tree nuts– Shellfish, finfish

• Resolution in childhood– Cow’s milk, egg, wheat, and soy– ~70% by 10 years– ~80% by age 16 years

JACI 2014;133:291-307, JACI 2010;125:S116-125.

Pathophysiology

• Failure for the development of oral tolerance– Tolerance: a robust T cell-mediated

hyporesponsiveness to antigen encountered in the gut

– Recognize intestinal pathogens, commensal microbes, and food antigen

– Sensitization via the oral vs. cutaneous route (bypasses tolerance induction)

Mucosal Immunology 2012;5:232–239, JACI 2012;129:1570-1578

Bauer C. Chapter 3: Specific Immune Responses. ACAAI Review for the Allergy and Immunology Boards—Second Edition. 2013 by American College of Allergy, Asthma & Immunology.

Diagnosis

http://www.alk-abello.com/US/products/diagnostics/Pages/SectionFront.aspx

Question #2

On a vacation in Florida, a 12-year-old boy orders mahi mahi in a restaurant. Within 20 minutes of eating it, he develops abdominal cramps, vomiting, swelling of the tongue, and trouble breathing. He has eaten fish all of his life. Skin testing to all white fish is negative.

Question #2

What is the cause of his illness?A. Finfish allergyB. Shellfish allergyC.Scromboid fish poisoningD.Gastroenteritis

Answer #2C. Scombroid fish poisoning

– Query if others “got sick” – Eating spoiled (decayed) fish that release

histamine-like chemicals– Mackerel, tuna, bluefish, mahi-mahi, bonito,

sardines, anchovies, and related species of fish

It’s often in the history. Diagnostics are supportive!!!

Diagnostics

• Detailed familiarity with the gamut of food-induced allergic disorders

• Understanding of the pathophysiology (timing, symptoms, etc.)

JACI 2014;133:291-307.

Adverse Food Reactions

Immune mediated

IgE mediated

Acute urticaria/

angioedema, oral allergy syndrome,

rhinitis, asthma,

anaphylaxis, food

dependent exercise induced

anaphylaxis

Non-IgEmediated or

Cell mediated

FPIES, celiac disease, dietary protein

proctitis, allergic contact

dermatitis

Mixed

Atopic eczema, eosino-philic

gastro-intestinal disease

Non-Immune mediated

Metabolic

Lactose intolerance,

galacto-semia, EtOHintolerance

Pharmaco-logic

Caffeine, tyramine

Toxic

Scromboidor other

food poisoning

Other

Sulfites, food

aversion, anorexia, auriculo-temporal

syndrome, gustatory rhintitis

Diagnostics

• Specific IgE testing– Sensitization does not necessarily imply

reactivity– RAST vs. ImmunoCAP– Higher specific food IgE (and skin test size)

probability; not severity of reaction– Skin prick testing has a high negative

predictive value (>90%)

JACI 2014;133:291-307.

Diagnostics

• Component-resolved diagnostics (CRD)– Testing for specific protein within foods

• Labile versus stable• Binding to conformational versus linear epitopes

Food Labile StabilePeanut Ara h8 Ara h1/2/3/6/9

Cow’s milk Whey CaseinEgg Ovalbumin Ovomucoid

JACI 2014;133:291-307, JACI 2010;125:S116-125

Diagnostics• What about cross reactivity? Cross

contamination?Allergy to: Related food: Clinical Reaction Rate

Peanut Most legumes 5%Tree nut Other tree nuts 35%Fin fish Other fin fish 50%Shellfish Other shellfish 75%

Grain Another grain 25%Cow’s milk Goat/sheep milk

Mare milkBeef

>90%5%

10%

JACI 2014;133:291-307. Ann Allergy Asthma Immunol 2017;118:591-596

?

Diagnostics

• Diagnostic gold standard– Oral food challenge (OFC)

• Gradually feeding a possible allergen under medical supervision to determine tolerance or clinical reactivity.

• Double-blind• Placebo-controlled

JACI 2010;125:S116-125.

Diagnostics

• Common uses for oral food challenges (OFC)– Tolerance to the food antigen

• Extensively heated or “baked” food antigens–Milk and egg–Denatures conformational epitopes

JACI 2014;133:324-334.

Diagnostics• Unsafe methods

– Intradermal testing• Un-useful methods

– Total IgE– Atopy patch testing*

• Unproven methods– Lymphocyte stimulation– Facial thermography– Gastric juice analysis

– Endoscopic allergen provocation

– Hair analysis– Applied kinesiology– Provocation neutralization– Allergen-specific IgG/G4– Cytotoxicity assays– Electrodermal test (Vega)– Mediator release assay

JACI 2010;126:S1-58.

Prevention

Question #3

• When should you consider peanut protein introduction in a child with severe eczema?A. 4 to 6 monthsB. 11 to 12 monthsC. 1 to 2 years oldD. >2 years old

Answer #3

A. 4 to 6 months

Prevention• 2000 AAP• 2008 AAP• 2010 NIAID

– Breast-feeding– Maternal diet restriction– “Insufficient evidence exists for delaying

introduction of solid foods, including potentially allergenic foods beyond 4 to 6 months of age.”

JACI 2010;126(suupl)S1-58

• Subjects: 640 high-risk UK infants (4-11 months)• Methods: Randomized to consume peanut (6 g of peanut

protein/week; equivalent to 24 peanuts or 3 teaspoons of peanut butter/week) or avoid– Challenged at age 5

NEJM 2015 Feb 26;372(9):803-13

Prevention

NEJM 2015 Feb 26;372(9):803-13

Prevention

• LEAP Take home: Early consumption of peanut in high risk infants with severe eczema or egg allergy reduced the development of peanut allergy by 81%

Prevention

• Effect of avoidance on peanut allergy after early peanut consumption (“LEAP-On”)

• Subjects: 550 children from the LEAP trial (all assigned to avoid peanut for 1-year)

• Results: – No significant change in allergy prevalence

during the year of avoidance• Take home: Absence of reactivity is maintained

NEJM 2016;374:1435-1443

Prevention• Randomized trial of introduction of

allergenic foods in breast-fed infants (EAT Study)

• Subjects: UK exclusively breast fed infants (n=1,303 ) enrolled at 3 months and followed to 1 to 3 years of age

• Methods: Randomized to consume highly allergenic foods at 3 months versus 6 months of age

NEJM 2016; 374:1733-1743

Prevention

• Results:– No statistically significant difference in food

allergy in the intention to treat group– Per protocol analysis suggested that early

introduction reduced the risk of any food allergy (2.4% vs. 7.3%)(peanut and egg)

– No episodes of anaphylaxis– ITT vs PP analysis? Feasibility?

NEJM 2016; 374:1733-1743

Prevention

• 2017 NIAID Expert Panel Addendum Guidelines– 64 publications

JACI 2017;139:1

Prevention

• Addendum 1:• Severe eczema, egg allergy or both

– Obtain peanut IgE or skin prick test– Earliest Age of introduction: 4-6 months

JACI 2017;139:1

JACI 2017;139:1

Prevention

JACI 2017;139:1

• Editorial:– “no statistically significant relationship between

the peanut [serum] IgE level and the baseline challenge outcome”

– “Many babies without peanut allergy will have positive IgE test results, sometimes at high levels, and will be declared to have peanut allergy if they are not able to access the specialty care for further testing.”

Prevention

• 6-7 g of peanut protein/week divided in 3 or more feedings– 1 peanut kernel = 250 mg peanut protein– 2 g = 2 teaspoons of peanut butter 3x/week– 2 g = 21 pieces of Bamba

JACI 2017;139:1

Prevention

• Addendum 2:• Mild to moderate eczema

– Introduce peanut containing foods– Earliest Age of introduction: 6 months

JACI 2017;139:1

Prevention

• Addendum 3:• No eczema or food allergy

– Introduce peanut containing foods– Earliest Age of introduction: age appropriate

and in accordance with family preferences and cultural preference

JACI 2017;139:1

Treatment

• Avoidance!!!• Epinephrine autoinjector

– EpiPen– Auvi-Q (0.3 mg, 0.15 mg, and 0.1 mg)– Generic epinephrine autoinjector– 2-pack

JACI 2014;133:291-307.

Treatment• Education

– Cross-contamination– Traveling and restaurants– Schools– Label reading– Resources– Medical ID– Substitutes for food being eliminated– Recognizing and treating anaphylaxis (action plan)

Food Allergy

Question #4

• Which of the following stressors was noted in a recent study in 45% of children with food allergies?A. BullyingB. Restaurant phobiaC. Limited food choices around friendsD. Anxiety about epinephrine autoinjector use

Pediatrics 2013;131:e10-17.

Answer #4

A. Bullying– In most of the cases, parents were not aware– Children had lower quality of life scores and

increased anxiety• With parental awareness, the quality of life

was less affected

Pediatrics 2013;131:e10-17.

Question #5

• All patients with food allergy, especially peanut allergy, should be started on oral immunotherapy as soon as possible. It is an effective and safe, FDA approved treatment for food allergy.

• True or False

Answer #5

• False

Treatment

• Oral immunotherapy (OIT)– (Extensively heated or baked form)– Lyophilized or pure form of allergen

• Sub-lingual immunotherapy (SLIT)• Epicutaneous immunotherapy (EPIT)

Treatment

• Baked egg food challenge (HealthNuts study)– Infants with oral food challenge (OFC)

confirmed raw egg allergy (n=140) were offered baked egg challenges at age 1

– At age 2, raw egg OFC was repeated

JACI 2014;133:485-491

Treatment• Baked egg food challenge (continued)

– Frequent ingestion increased the likelihood of tolerance

JACI 2014;133:485-491

Treatment• Baked cow’s milk food challenge

– Baked milk tolerant initially were 28 times more likely to become raw milk tolerant • Compared with baked milk–reactive subjects

– (P < .001)• Over the 3-year study

JACI 2011;128:125-31

Treatment• OIT for hen’s egg (CoFAR)

– Randomized, DBPC trial of 55 children, 5-11 years olds– Maintenance dose of 2,000 mg egg protein– 75% of treatment group passed OFC at 22 months– 28% of treatment group had sustained unresponsiveness

at 24 months (2 months of avoidance)– Safety and quality-of-life issues

• No severe adverse events were reported (oropharyngeal symptoms common)

• (Eosinophilc esophagitis reported)

N Engl J Med. 2012 Jul;367(3):233-43, Allergy. 2007;62(11):1261, Ann Allergy Asthma Immunol. 2011;106(1):73.

Treatment• OIT for peanut (DEVIL study)

– Randomized, DBPC trial of 40 children with peanut allergy, aged 9-36 months

– Treatment group given 300 or 3000 mg maintenance dose of peanut OIT

– Sustained unresponsiveness 4 weeks after OIT seen in 29 of 37 (78%) of the intent-to-treat population

• 300 mg group – 85%; 3000 mg group 71%; p 0.43– 95% of the subjects were affected by AEs that were likely

related to OIT (85% mild; 15% moderate; none severe)

J Allergy Clin Immunol. 2017;139(1): 173.

Treatment• Phase 3 PALISADE Trial

– Peanut ALlergy oral Immunotherapy Study of AR101 for DEsensitization

– AR101 is a novel, investigational oral biologic drug– Patients ages 4–17

• 67.2% of AR101 subjects tolerated at least a 600-mg dose of peanut protein in the exit food challenge (after 6 months of 300 mg peanut protein treatment)

• 4.0% of placebo patients (p

Treatment

• OIT limitations– Full maintenance dose cannot be achieved

due to allergic symptoms – Systemic reactions occur at previously

tolerated doses (exercise, viral illness)– Sustained unresponsiveness (a cure) is not

likely attainable with the therapies currently under study

J Allergy Clin Immunol. 2009;124(6):1351, J Allergy Clin Immunol. 2016;137:973

Treatment

• Sub-lingual immunotherapy (SLIT)– Extract form of allergen– Not absorbed systemically– Compared to OIT

• Lower rates of systemic reactions• Lower doses of antigen needed• Less effective

– Start with SLIT, then transition to OIT

J Allergy Clin Immunol. 2012 Feb;129(2):448-55

Treatment

• Epicutaneous immunotherapy (EPIT)– Epicutaneous immunotherapy for the

treatment of peanut allergy in children and young adults

– 74 subjects with peanut allergy (4-25 years) – Placebo, Viaskin Peanut 100 mg (VP100), or

Viaskin Peanut 250 mg (VP250)

J Allergy Clin Immunol. 2016; Oct. Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

Treatment

• Food challenges at 52-weeks– 12% placebo-treated participants– 46% VP100 participants– 48% VP250 participants– 14.4% of placebo doses and 79.8% of VP100

and VP250 doses resulted in reactions (predominantly local patch-site and mild reactions (P = .003))

J Allergy Clin Immunol. 2016; Oct. Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

Treatment

• Food immunotherapy recommendations– Not yet an FDA-approved treatment!– Further studies are necessary

• Optimal schedule• Optimal dose• Optimal duration• Maintenance of efficacy

J Allergy Clin Immunol. 2016;137:973 J Allergy Clin Immunol. 2009;124(6):1351, ]

Summary1. IgE mediated food allergies are due to a specific

immune response, occur reproducibly after ingestion of a food (usually immediately), and produce a specific spectrum of symptoms

2. 8 foods account for 90% of all food-allergic reactions3. Cow’s milk, egg, soy, and wheat allergies commonly

resolve4. Food allergy occurs due to the failure to development

oral tolerance

Summary5. Sensitization on food percutaneous skin testing or specific

IgE testing does not necessarily imply clinical reactivity6. For children at high risk for peanut allergy, IgE testing and,

if appropriate, introduction is recommended as early as 4 to 6 months of age.

7. Baked cow’s milk and egg challenges in appropriately selected patients can expedite the development of tolerance

8. Oral, sub-lingual, and epicutaneous immunotherapy are still investigational treatments with more data needed.

Thank you!!!

• Questions?• [email protected]