Food allergy from infancy through adulthood Presented by Pornsiri Sae-lim, MD. November 27, 2020

1. Food Allergy from Infancy
Through Adulthood
Pornsiri Sae-lim , MD
Pediatric Allergy and Immunology Department
King Chulalongkorn Memorial Hospital

2. Objective
• To understand the natural course and etiology of food allergy from infancy through adulthood
• To identify food-allergic disorders that present differently according to age group
• To provide food allergy management as appropriate for different age groups

3. Outline
• EPIDEMIOLOGY
• ETIOLOGY
• MANIFESTATIONS AND DISORDERS
• NATURAL COURSE
• MANAGEMENT ACROSS THE LIFE COURSE
• TREATMENT

4. EPIDEMIOLOGY
•Self-reported food allergy typically overestimates prevalence compared
with estimates based on a diagnosis determined by allergy testing
•The types of food-allergic reactions included in estimates of food allergy
prevalence can also affect the estimate

5. Ruchi S. Gupta, MD, MPH, PEDIATRICSVolume 142, number 6, December 2018:e20181235
• Large, population-based survey estimates childhood FA prevalence and
severity of all major allergenic foods
• US households between 2015 and 2016, obtaining parent-proxy responses
for 38 408 children
• Reported symptoms clearly consistent with acute, IgE-mediated
reactions—excluding probable PFAS
• Self-reported food allergy typically overestimates prevalence compared
with estimates based on a diagnosis determined by allergy testing

6. • FA prevalence was 7.6% (95% confidence interval: 7.1%–8.1%) after excluding 4% of children whose
parent-reported FA reaction history was inconsistent with immunoglobulin E–mediated FA
• The most prevalent allergens were peanut (2.2%), milk (1.9%), shellfish (1.3%), and tree nut (1.2%)
• 42.3% reported ≥ 1 severe FA
• 39.9% reported multiple FA
• 19.0% reported ≥ 1 FA-related emergency department visit in the previous year
• 42.0% reported ≥1 lifetime FA-related emergency department visit
• 40.7% had a current epinephrine autoinjector prescription
Ruchi S. Gupta, MD, MPH, PEDIATRICSVolume142, number 6, December 2018:e20181235

8. Ruchi S. Gupta, MD, MPH, Prevalence and Severity of Food Allergies Among US Adults, JAMA Network Open.
2019;2(1):e185630. doi:10.1001/jamanetworkopen.2018.5630

9. • The rate of food allergy
• 2.8% in infants under age 1 year
• peaked to 10% at age 2 years
• 7.1% in adolescents aged 14 to 17 years.
• Cow’s milk was the most common food allergen in early life
• approximately 50% of convincingly food-allergic <1-year-olds
• 40% of food-allergic 1- to 2-year-olds
• 30% of food-allergic 3- to 5-year-olds
• Among children aged 6 to 10years, peanut surpassed cow’s milk allergy in prevalence
• among 1 in 3 food-allergic children
• By early adolescence
• tree nut & shellfish allergies also exceeded cow’s milk allergy in prevalence
• each present in approximately 1 in 5 food-allergic children

10. • Cross-sectional survey study of US adults
• Administered via the internet and telephone from October 9, 2015, to September 18, 2016.
• Self-reported food allergies were the main outcome and were
• Considered convincing if reported symptoms to specific allergens were consistent with IgE-
mediated reactions
Ruchi S. Gupta, MD, MPH, JAMA Network Open. 2019;2(1):e185630.
doi:10.1001/jamanetworkopen.2018.5630

11. •Concomitantly surveyed 40,443 adults (aged 18 years and older)
•Convincing food allergies in 10.8% (95% CI: 10.4%-11.1%), with an additional 8.2%
reporting reaction symptomatology deemed inconsistent with an IgE-mediated
reaction
•The most common allergies were
• shellfish (2.9%; 95%CI, 2.7%-3.1%)
• milk (1.9%; 95%CI, 1.8%-2.1%)
• peanut (1.8%; 95%CI, 1.7%-1.9%)
• tree nut (1.2%; 95%CI, 1.1%-1.3%)
• fin fish (0.9%; 95%CI, 0.8%-1.0%). visit

12. Ruchi S. Gupta, MD, MPH, JAMA Network Open. 2019;2(1):e185630.
doi:10.1001/jamanetworkopen.2018.563

13. • Among food-allergic adults, 51.1% (95%CI, 49.3%-52.9%) experienced a severe
food allergy reaction
• 45.3%(95% CI, 43.6%-47.1%) were allergic to multiple foods
• 48.0%(95% CI, 46.2%-49.7%) developed food allergies as an adult
• with shellfish allergy responsible for the largest number
• 24.0% (95%CI, 22.6%-25.4%) reported a current epinephrine prescription
• 38.3%(95%CI, 36.7%-40.0%) reported at least 1 food allergy–related lifetime
emergency department
Ruchi S. Gupta, MD, MPH, JAMA Network Open.
2019;2(1):e185630. doi:10.1001/jamanetworkopen.2018.5630

14. Ruchi S. Gupta, MD, MPH, JAMA Network Open.
2019;2(1):e185630. doi:10.1001/jamanetworkopen.2018.5630

15. • At least 1 in 10 US adults are food allergic
• Nearly 1 in 5 adults believe themselves to be food allergic
• 1 in 20 are estimated to have a physician-diagnosed food allergy
• Approximately half of all food-allergic adults developed at least 1 adult-onset
allergy, suggesting that adult-onset allergy is common in the United States among
adults of all ages
• Wide variety of allergens, and among adults with and without additional,
childhood-onset allergies
Ruchi S. Gupta, MD, MPH, JAMA Network Open.
2019;2(1):e185630. doi:10.1001/jamanetworkopen.2018.5630

16. Ruchi S. Gupta, PEDIATRICS Volume 142, number 6, December 2018:e20181235
Ruchi S. Gupta, JAMA Network Open. 2019;2(1):e185630. doi:10.1001

17. Ruchi S. Gupta, PEDIATRICSVolume 142,number 6, December 2018:e20181235
Ruchi S. Gupta, JAMANetwork Open.2019;2(1):e185630.doi:10.1001
Childhood :
• milk and egg, are more likely to resolve
• peanut, tree nuts, fish, and shellfish allergies frequently persist into
adulthood
Adult
• High rates of new-onset allergy to typical “childhood” allergens (eg, milk
22.7%, egg 29%, wheat 52.6%, and soy 45.4%)

19. DOES ETIOLOGY DIFFER
BY AGE?

20. ETIOLOGY
• Lack or loss of tolerance to foods
• Result of numerous genetic and environmental factors
• Immune alteration and/or digestion/absorption of the foods may influence allergy
•infants and children are at greater risk than adults for developing food allergies
• “ Dual allergen exposure hypothesis ” can result in allergic sensitization
•non ingestion exposures via the skin, especially on inflamed skin
•lack of oral exposure

21. ETIOLOGY
• The potential importance of AD control and prevention among children to reduce the risk of
food allergy
• Children with AD and positive IgE antibodies to specific foods have a fairly significant risk
of developing acute food-allergic reactions when foods are removed from their diet to treat
the AD
• 1 in 5 patients with food-triggered AD & no previous history of IgE-mediated food
hypersensitivity reactions developed new immediate reactions to a variety of newly avoided
foods with nearly one-third of such patients experiencing anaphylaxis
• the airway is also a powerful sensitizing route of exposure because PFAS occurs despite
ingestion of fruits with the proteins that are homologous to the pollen

22. ETIOLOGY
• adult-onset food allergy
• alteration in gut permeability, skin and lung exposure as a sensitizing route, and loss of
desensitization
• acid suppressors may be a risk factor for adult food allergy
• Food dependent, exercise-induced anaphylaxis occurring to otherwise tolerated foods (another
example of alteration in gut permeability) suggest that adults may be prone to gut-level disturbances
• Occupational/airborne & skin exposure may sensitize adults
• soy allergy may be triggered by pollen exposure
• alpha-gal syndrome from tick bites
• milk/cheese, wheat, and soy allergies in adults who use cosmetics and skin-care products
• Periods of no oral exposure
• Shellfish or tree nuts, are not eaten regularly,loss of a desensitized state may be an explanation
• New-onset acute allergic reactions to milk in atopic adults who avoided milk

23. MANIFESTATIONS AND
DISORDERS

24. Acute allergic reactions and anaphylaxis
• Fatalities from allergic reactions are rare overall, but appear to be slightly more
common among children
• Infants less than 1 year of age seem to have milder symptoms compared with older
•main symptoms being hives, rash, or vomiting
•less commonly respiratory or cardiovascular
• History of at least 1 “severe” reaction over the lifetime
•42.3% (95% CI: 39.1%-45.4%) of US food-allergic children
•51.1% (95% CI:49.3%-52.9%) of US food-allergic adults

25. Acute allergic reactions and anaphylaxis
• Foods with the highest rates of severe reactions were identical (child rate/adult rate): peanut
(59.2%/67.8%), tree nut(56.1%/61.3%), shrimp (51.1%/56.6%), and fish (49.0%/56.5%)
• Major food allergens (milk, egg, wheat, soy, peanut, tree nuts, fish, shellfish, sesame) had severe reaction
rates over 27%
• Gupta et al : the rates of severe reactions to
Milk were 25.3% in children versus 39.3% in adults,
Egg were 28.1% in children versus39.4% in adults
• Childhood-onset allergies, suggesting persistence of the more severe phenotypes
Severity & anaphylaxis rates across the age spectrum, but the triggers of severe reactions are
substantially similar

26. Food protein induced allergic proctocolitis
(FPIAP)
• considered a disease of infancy that resolves in the first year of life
• eosinophilic colitis (as a specific diagnosis) & colonic eosinophilia (from a variety of triggers or part of
systemic illness) are well described in adults
• grouped among eosinophilicgastrointestinal disorders, with varied symptoms and etiologies
• some patientspresent with blood in the stool and associationwith atopy and food allergy
• specific relationship between FPIAP of infancy to the food-related subtypes of eosinophilic colitis in adults
remains unexplored
Scott H. Sicherer, MD, Food Allergyfrom Infancy Through Adulthood,J ALLERGYCLINIMMUNOLPRACTVOLUME8, NUMBER6

27. Food protein induced enterocolitis (FPIES)
• “acute” FPIES reaction ** mimicking sepsis**
• Typically presents in infancy, with repetitive protracted vomiting
• Begins approximately 1 to 4 hours after ingestion of the trigger food
• Accompanied by lethargy; pallor and diarrhea may follow
• Severe reactions can progress to hypothermia, methemoglobinemia, acidemia, &
hypotosion
• “chronic” form of FPIES may occur when the offending food is ingested regularly
• The triggers are classically milk, soy, oat, and rice, but
• Triggers vary internationally, fish being a more common trigger in Italy and Spain

28. Food protein induced enterocolitis (FPIES)
• Reports of FPIES in adults are increasing
• the trigger being previously tolerated
•mostly shellfish, fish, milk, egg, wheat
•symptoms similar in timing and pattern to infant FPIES
•predominantly females (infant FPIES predominantly affects males)
•the natural course of FPIES in adults is also unexplored

29. Eosinophilic esophagitis (EoE)
• Children and adults may have different EoE presenting characteristics
• Infants and young children may experience reflux symptoms, vomiting, pain, and poor
growth
• older children, adolescents, and adults
• heartburn but
• dysphagia with solid/chunky foods
• chest pain
• experience
• food impaction

30. Eosinophilic esophagitis (EoE)
• Endoscopy and biopsy findings may differ with age, based on increasing fibrosis and stenosis
with time
• Adults are more likely to experience stenosis and require esophageal dilatation
• EoE appears to be persistent
• Ridolo et al : compared risk factors associated with EoE
• children - risks for refractory disease were female gender and high visual analog scale
scores at follow-up
• adults- risks were longer periods of follow-up, diagnostic delay, use of antibiotics during
infancy, food allergies

31. Atopic dermatitis (AD)
• about one-third of children with moderate-to-severe AD also have food allergy.
• Studies of diets that eliminate specific targeted foods or common food allergens in children
suggest that at least a subset of them may improve AD,
• The possible role of food allergy in adult AD is clearly understudied.
• no studies evaluating the role of food allergies triggering AD over the life course, and
overall

32. Pollen-food allergy syndrome (PFAS)/oral allergy
syndrome (OAS)
• Typically report oral or throat pruritus when ingesting raw fruits or vegetables that have proteins
homologous to the pollen protein
• Trigger food proteins are easily denatured by heat or digestion
• Not expected to present in infancy or early childhood before pollen exposure
• Prevalence rates overlap between children and adults
• review of the literature as of 2018 reported PFAS prevalence
• 4.7% to more than 20% among children
• 13% to 58% among adults
• PFAS/OAS are similar across the life coursethe & persistent, studies have not reported long-term
outcomes over the lifespan

33. NATURAL COURSE
• IgE-mediated allergies
•milk, egg, wheat, and soy typically resolve in childhood
•peanut, tree nuts, fish, and shellfish are generally persistent
•the majority of adult food allergies begin in childhood and are persistent
• None IgE-mediated allergies of infancy and childhood—
•FPIAP and FPIES—usually resolve
•EoE and PFAS appear to be persistent

35. MANAGEMENT ACROSS THE LIFE COURSE
• Avoiding the allergen
• Preparing to recognize and treat an allergic reaction or anaphylaxis
• The responsibility for managing food allergy changes dramatically over the life course

36. •Data from recent US population-based surveys indicate
• Patient-reporting of having a current epinephrine prescription declines with age
• Although approximately 2 in 3 children/adolescents with physician-confirmed food
allergy reported
• Epinephrine autoinjector prescription dropped to 1 in 3 among patients aged 50 up
• By age 60, fewer than 1 in 3 patients with physician-confirmed food allergy and a
history of food allergy related ED visits reported a current epinephrine autoinjector
prescription

38. Treatment
• Safety and efficacy are a consideration when considering the age group
• 3 main forms of immunotherapy for food allergy
• Oral immunotherapy [OIT]
• Sublingual immunotherapy [SLIT]
• Epicutaneous immunotherapy [EPIT]
• Adding adjuvants and anti-IgE to either enhance the efficacy or safety of food
immunotherapy
A. Wesley Burks,MDJ ALLERGYCLINIMMUNOLVOLUME141, NUMBER

41. OIT
• Variety of food allergens have been studied
• Most randomized controlled trials have focused on peanut, milk, and egg
• Escalating doses of the offending food, with the hope of slowly inducing desensitization or
possibly SU
• modulation of the immune response
• transition from allergen-specific IgE to IgG4
• Decreased basophil activation to allergen crosslinking,
• Increase in numbers of regulatory T cells

42. Peanut OIT

43. EGG OIT

44. Milk OIT

45. Safety of OIT
• Associated with more allergic side effects than other forms of immunotherapy
• induction of episodic anaphylaxis with dosing
• dose-limiting gastrointestinal side effects in approximately 20%
• eosinophilic esophagitis in less than 5% of clinical trial participants
• Dose adjustments are frequently required because of viral illness, exercise, or menses to
maintain a safe dosing profile
• retrospective review including 395 patients, of 240,351 doses
• 95 doses required epinephrine administration because of a severe reaction
• 298 (85%) patients were able to achieve maintenance dosing

46. EPIT
• a small allergen patch to the back or upper arm, with patches changed at 24-hour intervals over years of
therapy
• well tolerated with typically only mild skin irritation noted at the patch site for the majority of those treated
• investigated for the treatment of peanut & milk allergy
• Peanut allergy: clinical desensitization primarily in younger age groups and only associated with a modest
treatment response after 52 weeks

47. SLIT
• an allergen extract in the sublingual space (held under the tongue for 2-3 minutes and then swallowed) on
a daily
• well tolerated, with minimal side effects that are typically limited to oropharyngeal itching or tingling
• More than 98% of doses were tolerated without adverse reactions beyond the oropharynx, and no
epinephrine was required for symptoms.
• immunologic changes were seen in those with favorable responses by decreased peanut-specific basophil
activation and skin prick test results

49. comparison of SLIT with OIT
•peanut allergy
•Retrospective comparison : OIT was found to have more significant changes in
peanut-specific IgE and IgG4 levels
•Prospectively: increased food challenge threshold was found in both groups but
more so with OIT
•Specifically, a 141-fold increase in maximum tolerated dose was observed in
OIT-treated patients compared with a 22-fold increase in SLIT-treated patients

50. Treatment
• EPIT with a commercial product may be ineffective in older children
• OIT or SLIT may also be
• more effective or have longer lasting effects,
• induce prolonged remission in very young children compared with patients in other age groups
• OIT and SLIT have both shown promise in treating peanut and milk allergy, across
different ages
• In all ages with common food allergies >> Combination of SLIT and OIT may induce a
significant increase in challenge thresholds with fewer adverse event

51. Summury
• Remarkable t some aspects of food allergy such as
• common triggers of severe reactions : peanut, tree nuts, shellfish
• mild reactions : fruits and vegetables related to pollen sensitizationare
• Food allergy may also be similar over the lifespan.
• Etiology of newonset
• Management strategies must change with age to address
• New therapeutics emerge, it will be important to consider their potential impact at
different ages