Food allergy the old and the new Cindy Salm Bauer, MD, FAAAAI Division of Allergy and Immunology, Phoenix Children's Hospital Assistant Professor,

Transcription

1 Food allergy the old and the new Cindy Salm Bauer, MD, FAAAAI Division of Allergy and Immunology, Phoenix Children's Hospital Assistant Professor, Dept of Medicine, Mayo Clinic Arizona

2 None Disclosures

3 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 FDAapproved.

4 Background Definition Prevalence Natural Course Pathophysiology Diagnosis Prevention Treatment Overview

5 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

6 Adverse Food Reactions Immune mediated Non-Immune mediated IgE mediated Non-IgE mediated or Cell mediated Mixed Metabolic Pharmaco -logic Toxic Other Acute urticaria/ angioedema, oral allergy syndrome, rhinitis, asthma, anaphylaxis, food dependent exercise induced anaphylaxis FPIES, celiac disease, Heiner syndrome, dermatitis herpetiformis, dietary protein proctitis, allergic contact dermatitis Atopic eczema, eosinophilic gastrointestinal disease Lactose intolerance, galactosemia, EtOH intolerance Caffeine, tyramine Scromboid or other food poisoning Sulfites, food aversion, anorexia, auriculotemporal syndrome, gustatory rhintitis JACI 2014;133:

7 Prevalence 8 foods account for 90% of all foodallergic reactions: cow s milk, eggs, peanuts, tree nuts wheat, soy, fin fish, and shellfish JACI 2010;125:S

8 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.

9 Question #1 What is his diagnosis? A. Eosinophilic Esophagitis B. Oral Allergy Syndrome C.Multiple Food Allergy Syndrome D.Eosinophilic gastritis

10 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

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12 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: , JACI 2010;125:S

13 Mucosal Immunology 2012;5: , JACI 2012;129: 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)

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

15 Diagnosis

16 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.

17 Question #2 What is the cause of his illness? A. Finfish allergy B. Shellfish allergy C.Scromboid fish poisoning D.Gastroenteritis

18 Answer #2 C. 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!!!

19 Diagnostics Detailed familiarity with the gamut of foodinduced allergic disorders Understanding of the pathophysiology (timing, symptoms, etc.)

20 Adverse Food Reactions Immune mediated Non-Immune mediated IgE mediated Non-IgE mediated or Cell mediated Mixed Metabolic Pharmaco -logic Toxic Other Acute urticaria/ angioedema, oral allergy syndrome, rhinitis, asthma, anaphylaxis, food dependent exercise induced anaphylaxis FPIES, celiac disease, Heiner syndrome, dermatitis herpetiformis, dietary protein proctitis, allergic contact dermatitis Atopic eczema, eosinophilic gastrointestinal disease Lactose intolerance, galactosemia, EtOH intolerance Caffeine, tyramine Scromboid or other food poisoning Sulfites, food aversion, anorexia, auriculotemporal syndrome, gustatory rhintitis JACI 2014;133:

21 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:

22 Diagnostics Component-resolved diagnostics (CRD) Testing for specific protein within foods Labile versus stable Binding to conformational versus linear epitopes Food Labile Stabile Peanut Ara h8 Ara h1/2/3/6/9 Cow s milk Whey Casein Egg Ovalbumin Ovomucoid JACI 2014;133: , JACI 2010;125:S

23 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 milk Beef >90% 5% 10%? JACI 2014;133: Ann Allergy Asthma Immunol 2017l118:

24 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:S

25 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:

26 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.

27 Prevention

28 Question #3 When should you consider peanut protein introduction in a child with severe eczema? A. 4 to 6 months B. 11 to 12 months C. 1 to 2 years old D. >2 years old

29 A. 4 to 6 months Answer #3

30 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

31 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

32 NEJM 2015 Feb 26;372(9): Prevention

33 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%

34 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:

35 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:

36 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:

37 Prevention 2017 NIAID Expert Panel Addendum Guidelines 64 publications JACI 2017;139:1

38 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

39 JACI 2017;139:1

40 Prevention Editorial: no statistically significant relationship between the peanut 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. JACI 2017;139:1

41 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

42 Prevention Addendum 2: Mild to moderate eczema Introduce peanut containing foods Earliest Age of introduction: 6 months JACI 2017;139:1

43 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

44 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:

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

46 Question #4 Which of the following stressors was noted in a recent study in 45% of children with food allergies? A. Bullying B. Restaurant phobia C. Limited food choices around friends D. Anxiety about epinephrine autoinjector use Pediatrics 2013;131:e10-17.

47 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.

48 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

49 False Answer #5

50 Treatment Oral immunotherapy (OIT) (Extensively heated or baked form) Lyophilized or pure form of allergen Sub-lingual immunotherapy (SLIT) Epicutaneous immunotherapy (EPIT)

51 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:

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53 Treatment Baked egg food challenge (continued) Frequent ingestion increased the likelihood of tolerance JACI 2014;133:

54 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

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

56 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/su 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 % 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.

57 Treatment OIT for peanut safety and quality-of-life issues In general, about 20% withdraw from studies because of adverse events Local adverse reactions very common: oral itch, abdominal pain (most common reason to withdraw) J Allergy Clin Immunol. 2016;137:973, J Allergy Clin Immunol. 2009;124(2):292, J Allergy Clin Immunol Feb;133(2):500-

58 Treatment OIT limitations Full maintenance dose cannot be achieved due to allergic symptoms Systemic reactions occur at previously tolerated doses (exercise, viral illness) Tolerance (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

59 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 Feb;129(2):448-55

60 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

61 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

62 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, ]

63 Summary 1. 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 reactions 3. Cow s milk, egg, soy, and wheat allergies commonly resolve 4. Food allergy occurs due to the failure to development oral tolerance

64 Summary 5. Sensitization on food percutaneous skin testing or specific IgE testing does not necessarily imply clinical reactivity 6. 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.

65 Thank you!!! Questions?