Year-in-Review (2018) FOOD ALLERGY and Anaphylaxis. from the Journal of Allergy and Clinical Immunology: In Practice

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1 Year-in-Review (2018) FOOD ALLERGY and Anaphylaxis from the Journal of Allergy and Clinical Immunology: In Practice Scott H. Sicherer, M.D. Icahn School of Medicine at Mount Sinai, New York WSAAI Jan 22, :30-4:30

2 Disclosures No financial relationships to disclose (relevant to the presentation) Grants from NIAID/NIH, HAL allergy, Food Allergy Research and Education Associate Editor, JACI In Practice Royalties, UpToDate, Johns Hopkins U. Press

3 LEARNING OBJECTIVES Describe safety, efficacy and patient motivation regarding peanut oral immunotherapy. Investigate patients for mast cell disorders if they have severe sting reactions post immunotherapy Identify diagnostic factors for wheat associated exercise-induced anaphylaxis

4 Food Allergy Theme Issue 2018 Reviews/Reports on Food challenge (MacGinnite & Young) Unproven tests (Kelso) Prevention (Turner, Campbell, Boyle, & Levin) Treatments (Rachid, & Keet) Use of Amino Acid Formula (Meyer, Groetch,& Venter) Precautionary Labeling (Allen & Taylor) Skin test prior to LEAP? (Tang, Koplin & Sampson) Sibling and peanut allergy risk (Abrams, Chan & Sicherer) Allergist and Anaphylaxis/Food Allergy in School (Wang, Bingemann, Russell, Young, &Sicherer) Coordinated by Rima Rachid and Corinne Keet

5 *Audience response* IMMUNOTHERAPY A 12 year old has peanut allergy. He developed urticaria with introduction of peanut at age 1 year. At age 2 he had accidental ingestion of a peanut cookie estimated to contain 2 peanuts and he have facial hives and vomiting. He has had no reactions since with avoidance. Peanut IgE is 13 ku/l. Ara H 2 is 1.1 ku/l. Which of the following is the best advice when the family asks for peanut oral immunotherapy? A. Start OIT with store bought peanut B. Wait for FDA approved peanut oral immunotherapy C. Advise against treatment, await therapies other than OIT D. Perform a food challenge to peanut

6 J Allergy Clin Immunol Pract 2018;;6:476-85

7 Phase 2 study Ages 4-26 React <=143 mg (cumulative), aim to >=443, secondary 1043 mg

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9 One practice, 270 patients (26 Dx with OFC), ages 4-18 yrs, treated over 8.5 yrs One general protocol with periodic and patient-specific modifications, aim 3 Gram 79% completed escalation Epi treatment (ETR) in 63, isolated GI Sx in 101 Concluded results similar to research setting

10 Online survey OIT families, n=123, 83% peanut/nut 62% to reduce risk of fatal reaction 11% Reduce hassle of strict avoidance 9% to eat the food Estimated risk of death: 35% 1:1,000, 23% 1:10,000 Data suggests: 1 in 325,000 over 10 years Authors question if the OIT addresses the goals

11 191 children age 4-12 on OIT QOL survey at intervals in process Matched controls without OIT Deterioration of QOL in updosing, reversed in maintenance and overall better at follow up.

12 What would the clinical benefit be of some degree of increased threshold to peanut? Used data on contamination levels and exposure modeling (cookies, snack chips, ice cream, snack cakes). An increased threshold from 100 mg to 300 mg reduces the risk of a reaction by 95%

13 Mathematical modeling with multiple assumptions Avoidance of peanut precautionary labeling carries individual burdens and costs ($182M per death prevented) A single 1.5 mg oral food challenge then allowing consumption of precautioned labeled foods would be cost effective

14 Does speed of moving from baked milk to baked cheese to milk in rice pudding to whole milk affect outcome for those who can tolerate baked forms? 136 children studied, 93% did not tolerate whole milk and had escalation at 6 or 12 month intervals Exposure was associated with increasing immune modulation (increased Treg, decreased IgE, increased IgG) and ability to tolerate less heated forms, but timing had no advantage.

15 2 year follow up minimum This group allowed baked milk failures to eat some tolerated amount 99/206 passed ;19/107 who failed were told to avoid Success: younger, lower IgE, passing Concluded: Mostly successful but can have late reactions

16 Baked Potpourri Reviewed 84 baked milk OFCs 72% passed Skin tests did not distinguish Serum tests did, much overlap, less passing over 8 (LR, 3), most passing under 3 ku/l. Reviewed 90 positive baked food challenges Milk more severe Symptom Baked milk Baked egg Cough 29% 8% Wheeze 29% 3% Abdominal pain 4% 39% Vomit 4% 23%

17 30 year old severe AD Anaphylaxis to corn, generalized urticaria to pistachio on OFC (2 nuts) Started dupilumab for sever AD After 3 month treatment, OFC to pistachio and corn passed

18 Epidemiology, Risks Factors, Prevention

19 Used HealthNuts cohort 5276, population-based Australian study, had food challenges at ages 1 and 4. Outcome MD-diagnosed asthma at age 4 yrs Relative Risk 95% CI 1 food age >1 food, age Food plus eczema age Transient egg allergy Persistent egg allergy Lesson: Worry about Asthma if food allergic, esp as above ~triple risk

20 Although food allergy appears to have increased (in Australia more anaphylaxis), sensitization seems to have not Australian high risk infant cohorts (family history of allergy) 15 years apart ( ; ) No difference in sensitization rates Could be: more allergy among low risk, increased manifestation of allergy among those sensitized, more high risk infants. Or awareness?

21 Australian survey of year olds, n=4991, including OFCs Objective: explore risk factors for food allergy Key associations: Odds ratio 95% CI Male Early eczema Asian versus Caucasian parents Born in Asia versus Australia Multiple atopy family members versus Dog exposure

22 Singapore: Does timing of food allergen introduction relate to food allergy outcomes? 1152 mother-infant pairs Several allergens are commonly given after 10 months: egg- 49.6%, peanut-88.7%, shellfish- 90.2%. Allergy to these foods was low and not associated with timing of introduction, even when adjusting for breast-feeding and eczema. Risk factors: eczema, family allergy history Rules may not apply across cultures?

23 Anaphylaxis *Audience response* A 47 year old completed 5 years of venom immunotherapy for severe sting anaphylaxis. One year after completing immunotherapy he is in the garden and is stung. He develops severe anaphylaxis. What testing is important in this scenario? A. Serum IgE to venoms B. Tryptase level C. Comprehensive testing for mast cell disease D. Skin test to venom

24 VIT is often stopped after 3-5 years This study focused on 19 patients (mean age 56 yrs, 90% male) who had severe sting reactions and post VIT discontinuation (after 4-17 yrs) had re-sting, with reaction, 18 again severe. 18 had clonal mast cell disorders and 8 with normal tryptase Lesson: This scenario should warrant investigation and lifelong treatment is warranted

25 10,184 anaphylaxis incidents over 10 years in 9 European countries(registry, online, via allergy programs) Percent of anaphylaxis treated with epinephrine varied regionally

26 27.1% of anaphylaxis treated by health care professionals received epinephrine and 10.5% received a second dose The rate doubled over the 10 years 14.7% of lay-treated anaphylaxis received epinephrine 66.9% of near-fatal anaphylaxis received epinephrine Conclusion: underuse

27 ED visit Evaluate ED anaphylaxis trends over a 10 year span using an administrative claims database, 100 million insurance enrollees 56,212 ED visits, noted increases in visits, ICU admission, intubation. Elderly. Need to identify why To ICU Intubated

28 Controversy if tryptase increases in food allergy 50 adults (age 18-39) up to 4 challenges 160 reactions (9% anaphylaxis), 45 placebo Tryptase rose above 11.4 ng/ml in 4/160 but rose above baseline in 63% reactions (median rise 25%), 0% placebo. Lesson: Rise related to severity, best time 2 hours

29 Beta blocker use has been (controversy) associated with more severe anaphylaxis 7 year review of ED anaphylaxis for any or multiple epinephrine injections 789 patients, 8% required more than one dose epinephrine, 11% were on beta-blockers (power for 10% diff) Beta No Beta OR 1 epi versus 0 9% 12% 0.73 (95% CI, ) 2 or more epi vs % 10% 1.26 (95% CI ) Message: Beta blocker use may not clinically significant with regard to need for epinephrine for ED anaphylaxis

30 *Audience response* Food Diagnostics A 27 year old experienced anaphylaxis with exercise. He had eaten a large bowl of pasta with meatballs and tomato sauce prior to the reaction but eats these foods routinely without a reaction and exercises without a reaction. Wheat skin test and IgE were negative. What is the best next step for diagnosis? A. Eat 2 bowls of pasta as a food challenge B. Treadmill test with and without eating a bowl of pasta C. Serum test for omega 5 gliadin D. Test for allergy to garlic, tomato

31 Investigated augmentation versus dose in WDEIA 71 patients underwent gluten OFC with/without exercise 61% reacted, in 37% of these, reaction was at rest. Dose for rest was median 48 Grams (8-80), with exercise, 24 G (4-80). Severity was higher with exercise. Omega 5 Gliadin was best predictor of reactivity

32 132 patients in 4 UK centers Significant delay in diagnosis, 69%>5 yrs (idiopathic) Cofactors exercise (80%, alcohol 25%) IgE level did not predict severity, negative routine tests (50% neg SPT) Gluten-free diet/no wheat with exercise only 67/69% reduction in reactions Lesson: Suspicion (check omega-5-gliadin [Tri a 19] IgE) and tricky to avoid

33 Take home from wheat studies Diagnosis of WAEIA is tricky-dose, exercise Tests may be negative Test IgE omega-5 gliadin, but not FDA cleared Consider in unexplained anaphylaxis with exercise

34 *Audience response* Eosinophilic Esophagitis Which of the following was reported in the Journal this past year regarding eosinophilic esophagitis (EoE)? A. EoE is highly prevalent in those with severe milk allergy B. Avoiding milk as a treatment for EoE may result in sensitization/allergy to milk C. People with EoE may have higher rates of non-allergic comorbid conditions than the general population D. Remission of a food as a trigger of EoE is uncommon

35 Milk is a major food trigger for EoE Objective: Assess for EoE in milk allergy Recruited (prospective) those with persistent/severe (anaphylaxis) milk allergy, 89 patients over 4 yrs (Brazil) Did endoscopy no matter what Median age 8 yrs, 34 (38%) had esophageal eosinophilia, 5 were PPI responsive. 29.4% had been asymptomatic, 23.5% had persistent typical symptoms, 23.5% had intermittent typical symptoms Lesson: Suspect EoE in significant milk allergy

36 705 subjects with EoE, age 6m-65 yrs [median, 11 yrs], 5 US sites (CoFAR) 9.5% gastrointestinal eosinophilia 1.5 yr diagnosis time gap, shorter if food allergy or eczema, longer if adult, white Symptoms: pain/vomit in young, dysphagia in adult EoE in 3% parents, 4.5% siblings Co-morbidity: allergy (91%), immune/infectious disorders (44%), neurodevelopmental disorders (30%), failure to thrive (21%). Lesson: index of suspicion, attention to co-morbidities

37 EoE potpourri Identified 9 pts from database of 1812 where food caused EoE and then remitted In other words, rare event Case report 38 year old EoE and allergic rhinitis, EoE resolved with removal of raw birch-related foods 5 patients taken off milk to treat EoE became clinically reactive/sensitized

38 Potpourri (Clinical Communications) A 12 year old is given an antihistamine for itchy mouth due to apple ingestion. He then develops hives and vomits. His mother says he is probably allergic to the antihistamine because every time he gets the antihistamine he gets hives. When she gave it to him previously for itching from mosquito bites he developed hives, and when she gave it to him for runny nose with a cold in the pollen season he also developed generalized hives and vomiting. Which of the following is a likely diagnosis? A. Allergy to antihistamine B. Apple anaphylaxis C. Cold urticaria D. Idiopathic anaphylaxis *Audience response*

39 Antihistamine Allergy!

40 Potpourri Cold with meat Studies suggest 26-41% with acquired cold urtucaria experience systemic reactions Survey respondents mostly (86%) noted rates <10% and only 14% of respondents always prescribe epi autoinjector Tested 5 vaccines for peanut, milk, egg but none detected

41 Potpourri 20 year old with 6 episodes anaphylaxis from sweet foods No positive tests Reaction to Coca-Cola on OFC OFC reaction to isolated sucrose and to isolated fructose (sucrose=glucose plus fructose) Neg OFC to other 3 other sugars Positive BAT to fructose in patient, not control 100 allergy clinic patients on government insurance surveyed 80% non-white, 39% Hispanic 72% reaction in past year Reasons for non-adherence diet/rx See if reacts (21%), not bad reaction (17%), confused about what to avoid (145) Forgot EAI-Just forgot (25%, not necessary all the time (24%)

42 More Potpourri 3 patients undergoing LEAP early peanut All were peanut sensitized Had isolated delayed vomit, lethargy 3 children, 1 adult Most impressive: Child neg tests-wheeze and angioedema at 6 hours (OFC) confirming several prior similar reactions Another child only positive to HDM, next day edema and generalized urticaria Adult with positive, 4 hour delay Mechanism unknown

43 More Potpourri Online survey via FARE and Food Allergy Canada Parent survey 218 peanut free and 716 peanut restricted schools, 209 Canada, 843 US QOL not better peanut-free but country differences Child has multiple fish allergy Anaphylaxis to crocodile Identified fish parvalbumin

44 And last

45 March 2019 Food Allergy Stay tuned Issue!!!

46 Thank You! Attendees but also Editors (Michael Schatz, Robert Zeiger, David Kahn) Managing Editor (Dawn Angel) Editorial Board Reviewers Readers AAAAI Leadership