Allergo-Immunology Hour

Food Allergy

JDPMD
Objectives
• To discuss food allergies in terms of:
• Epidemiology
• Pathogenesis
• Clinical manifestations
• Diagnosis
• Treatment
• Prevention
Food Allergy
• Adverse reaction to food – Any untoward reaction
following ingestion of a food or food additive

• Food intolerance – adverse PHYSIOLOGIC responses

• Food allergies – adverse IMMUNOLOGIC responses
• IgE mediated
• Non-IgE mediated
Pathogenesis
• Food intolerance – result of a variety of mechanisms
• Inability to properly breakdown food
• May be due to enzyme deficiencies
• Sensitivity to food additives
• Reactions to naturally occurring food chemicals

• Food allergy – predominantly Ig-E mediated or cell-mediated responses

Food Intolerance

Nowak-Wegrzyn, et al. (2016) Food Allergy and Adverse Reaction to Foods. In R Kliegman et al., Nelson Textbook of Pediatrics 20th ed. Elsevier
Epidemiology of Food Allergy
• Prevalence increased over the past 3 decades primarily in countries
with a Western lifestyle
• 1-10% worldwide prevalence
• US: 3.5% of the population and 1 in 13 children suffer from food allergies
• Asia: 4-5%
• Up to 6% of children will have allergic reactions to food in the 1st 3 yrs of
life
• 2.5% cow’s milk
• 1.5% eggs
• 1% peanuts
Boye, JI (2012) Food allergies in developing and emerging economies: need for comprehensive data on prevalence rates. Clinical and Translational Allergy.
Alison, et al., (2013) Food allergy in Asia: how does it compare? Asia Pac Allergy
Epidemiology of Food Allergy
• Majority of children (85%) outgrow their milk, egg, soy, or wheat
allergies

• Peanut, tree nut and shellfish allergies are typically more persistent
• Only 20% of children outgrow their allergy

Bird , JA , et al., (2015) Clinical Management of Food Allergy . J Allergy Clin Immunol Pract
 Pathogenesis of Food Allergy (IgE mediated)
Exposure to certain
allergens

Formation of food-specific
IgE antibodies

Antibodies bind to Fcε

receptors on mast cells,
basophils, macrophages,
and dendritic cells

Food allergens penetrate

mucosal barriers and reach
cell-bound IgE antibodies

Release of mediators
causing local and systemic
symptoms
Pathogenesis of Food Allergy
• Class 1 food allergens – allergens penetrating the GI barrier
• Class 2 food allergens – allergens partially homologous to plant pollens
penetrating the respiratory tract

Class 1 food allergens Class 2 food allergens

Any food Typically vegetable, fruit or nut
90% are from egg, milk, peanuts, tree proteins that are partially homologous
nuts, fish, soy and wheat with pollen proteins
Pathogenesis Non-IgE Mediated
• Lymphocytes, primarily food allergen–specific T cells, secrete
excessive amounts of various cytokines  “delayed,” more
chronic inflammatory process
• Affects the:
• Skin (pruritus, erythematous rash),
• Gastrointestinal tract (failure to thrive, early satiety, abdominal
pain, vomiting, diarrhea)
• Respiratory tract (food-induced pulmonary hemosiderosis)
Natural History of Food Allergy and Cross-Reactivity
between Common Allergens
Clinical manifestations
• Subdivided by target organ and immune mechanism
Clinical Manifestations: Gastrointestinal
• Predominantly cell-mediated hypersensitivities
• Irritability, vomiting, “spitting-up”, diarrhea, and poor weight gain
• Food protein-induced enterocolitis syndrome (FPIES)
• Manifests in 1st several months of life
• MC provoked by cow’s milk or soy milk
• Irritability, intermittent vomiting and protracted diarrhea
• Vomiting occurs 1 – 3 hrs after feeding
• Continued food exposure may lead to bloody diarrhea, abdominal distention,
anemia, and failure to thrive
Clinical Manifestations: Gastrointestinal
• Food protein-induced enterocolitis syndrome (FPIES)
• Similar symptoms seen in older infants and children
• Due to rice, oat, wheat, egg, peanut, nut, chicken, turkey, or fish
• FPIES usually resolves by 3 years of age
• Food protein-induced proctocolitis
• Present in first few months of life as blood-streaked stools in otherwise healthy
infants
• 60% occur in breastfed infants, with the remainder largely among cow’s milk or
soy protein based formulas
Clinical Manifestations: Gastrointestinal
• Food protein-induced enteropathy
• Manifests in first several months of life as diarrhea with steatorrhea and poor
weight gain
• MCC: Cow’s milk sensitivity
• Also associated with soy, egg, wheat, rice, chicken, and fish in older children
• Most severe form: Celiac disease
• 1:100 of US population
• Cell-mediated response to tissue transglutaminase deamidated gliadin (seen in wheat, rye,
barley)
• Extensive loss of absorptive villi with crypt hyperplasia  malabsorption
Clinical Manifestations: Gastrointestinal
• Eosinophilic esophagitis (EoE)
• May appear from infancy through adolescence; M > F
• Primarily cell-mediated
• Chronic GER, intermittent emesis, food refusal, abdominal pain, dysphagia,
irritability, sleep disturbance, and failure to respond to anti-reflux medications
• Confirmatory: Histopath findings of 15 eosinophils per high-power field during
treatment with PPIs
• Eosinophilic gastroenteritis
• Also occur at any age with similar symptoms as EoE
• Prominent weight loss or failure to thrive are the hallmarks of this disorder
Clinical Manifestations: Gastrointestinal
• Oral Allergy syndrome (Pollen-associated food allergy syndrome)
• Occur in many older children with birch and ragweed pollen-induced allergic
rhinitis
• Usually confined to the oropharynx  rapid onset of oral pruritus, tingling and
angioedema of the lips, tongue, palate, and throat
• May have sensation of pruritus in the ears and tightness in the throat
• Generally short lived; caused by local mast cell activation following contact with
fresh fruit and vegetable proteins that cross-react with pollen
• Acute gastrointestinal allergy
• Acute abdominal pain and vomiting with other IgE mediated symptoms from
other target organs
Clinical Manifestations: Cutaneous
• Common in infants and young children
Atopic dermatitis
• Form of eczema beginning in early infancy
• Characterized by pruritus, chronically relapsing course
• Associated with asthma and allergic rhinitis
• At least 30% with moderate-severe AD have food allergies

Acute urticaria and angioedema

• Most common symptoms of food allergy
• Very rapid onset (within minutes)
• Result from activation of IgE bearing mast cells by food allergens
Clinical Manifestations: Cutaneous
Perioral dermatitis
• A contact dermatitis caused by substances in toothpaste, gums, lipsticks and
medications
Perioral flushing
• Seen in infants fed citrus fruits
• Benzoic acid
• Usually benign
Clinical Manifestations: Respiratory
• Uncommon as isolated symptoms
Food-induced rhinoconjunctivitis
• Accompany allergic symptoms in other target otgans
• Typical allergic rhinitis symptoms: periocular pruritus and tearing, nasal
congestion and pruritus, sneezing, and rhinorrhea

Wheezing
• Occur in 25% of IgE-mediated food allergic reactions
• *Only 10% of asthma patients have food-induced symptoms
Clinical Manifestations: Anaphylaxis
• Food allergies are the single most common cause of anaphylaxis in the
US
• Rapid onset of cutaneous, respiratory, and GI symptoms with
cardiovascular symptoms including hypotension, vascular collapse, and
cardiac dysrhythmias
• Due to massive mast cell-mediator release
Diagnosis: Thorough Medical History
Symptoms

Adverse reaction?

Food intolerance or
Food allergic reaction?

Food allergy
 Diagnosis: Thorough Medical History
Establish:
1) Food suspected of Food allergy
provoking the reaction
and the quantity ingested
(2) Interval between
ingestion and the IgE or Cell-mediated
development of symptoms response
(3) types of symptoms
elicited by the Ingestion
(4) Prior similar symptoms Cell mediated
upon ingesting the suspected
food
(5) Inciting factors, such as IgE dependent
exercise disorders
(6) interval from last
reaction to the food
Diagnosis
• Prick skin tests and in vitro
laboratories for IgE sensitization
• A NEGATIVE skin test virtually
excludes IgE mediated food allergy
• However, children with POSITIVE
skin test do not react to the food
when ingested  need for more
definitive tests
• Quantitative IgE tests
• Food elimination and challenge
Management
Management
• Definitive studies must be performed before recommendations are
made for avoidance or the use of highly restrictive diets
• The use of broad exclusionary diets is not warranted since IgE-mediated
food allergies are generally specific
• No laboratory studies available to help identify food responsible for cell-
mediated reactions
• Elimination diet  Food challenge

• Food challenge:
• Suspected food eliminated from diet for 10-14 days (IgE) and up to 8
weeks (cell-mediated)
Treatment
• Identification and elimination of foods responsible for hypersensitivity
• Self-injectable epinephrine + written emergency plan
• Many food allergies are outgrown
• Periodic reevaluation
• Immunotherapy
• Anti-IgE treatment (Omalizumab)
Prevention
Thank You!