1. food and drink
2. food allergies

3/24/15
Food Allergy Update
What’s New in 2015
Jeffrey M Factor MD
Connecticut Asthma and Allergy Center
West Hartford, CT
Disclosures
Speaker’s Bureau- Mylan, Merck, Teva,
Meda Pharmaceuticals
Highlights for 2015
• What are risk factors for developing food
allergies?
• Primary Prevention of Food Allergies
• What’s new in in Food Allergy Practice
Parameters?
• Oral immunotherapy update
• Advances with other forms of treatment
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Outline
• Definition / differential diagnosis
• Prevalence of food allergies
• Anaphylaxis and management
• Specific food allergy disorders
• Making an accurate diagnosis of food allergies
• Risk factors and prevention
• Oral immunotherapy and novel treatments for
food allergy
N Engl J Med
Vol. 346, No 17
N Engl J Med
Vol. 346, No. 17
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Food Allergy: Immune Systemmediated Adverse Food Reaction
IgE
• • URTICARIA
ANGIOEDEMA
Mixed
Non-IgE
• ATOPIC DERMATITIS
• • EOSINOPHILIC
GASTRO-INTESTINAL
DISORDERS
PROTEIN-INDUCED
PROCTOCOLITIS/
ENTEROCOLITIS
• • RHINITIS
ASTHMA
• CELIAC DISEASE
• ANAPHYLAXIS
• CONTACT DERMATITIS
• ORAL ALLERGY SYNDROME
• DERMATITIS
HERPETIFORMIS
• FOOD-DEPENDENT EXERCISE INDUCED ANAPHYLAXIS
• HEINER’S SYNDROME
Differential Diagnosis:
Non-Immune Mediated Adverse Food Reactions
• Toxic/Pharmacologic
Food poisoning
Scombroid fish poisoning
Ciguatera fish poisoning
Histamine
Tyramine
Caffeine
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Differential Diagnosis:
Non-Immune Mediated Adverse Food Reactions
• Non-Toxic/Intolerance
Lactase deficiency
Fructose intolerance
Galactosemia
Pancreatic insufficiency
Gallbladder/Liver disease
Panic/Anxiety
Depression, anorexia, bulimia
Hiatal hernia; GERD
Gustatory rhinitis
Auriculotemporal syndrome
Food Allergens
Children (6-8% affected)
• • • • • • • • Milk
Egg
Peanut
Soybean
Wheat
Tree nuts
Fish
Shellfish
Adults (3.5-4% affected)
• • • • • Peanut
Tree nuts
Fish
Shellfish
Fruits/vegetables in OAS
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Prevalence of Food AllergyGeneral Population
Cow’s Milk
Egg white
Peanut
Tree Nuts
Fish
Shellfish
Overall
Young Children
2.5%
1.3%
1.4 %
0.2%
0.1%
0.1%
6%
Adults
0.3%
0.2%
0.6%
0.5%
0.4%
2%
3.7%
Prevalence
• Prevalence continues to rise in children: there has been
an 18% increase in food allergies in past 15 years
• Peanut allergy: The rate of 1.4% in 2010 is more than
triple the rate of 0.4% in 1997
• 40% of peanut reactions are severe and potentially lifethreatening
• 30% of food allergic individuals are clinically reactive to
more than one food
Food Anaphylaxis
• Definition: an acute systemic allergic
reaction that is potentially fatal
• The opposite of prophylaxis “without or
against protection”
• Onset of symptoms seconds to minutes
(up to 2 hrs) following ingestion
• Prior reactions may have been milder
• Very unpredictable in its clinical
presentation and outcome
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Patterns of Anaphylaxis
• Uniphasic
– Rapid onset, symptoms resolve within hours
of treatment
• Biphasic
– Symptoms resolve after treatment but return
between 1 and 72 hours later (usually 1-3
hours)
• Protracted
– Symptoms do not resolve with treatment and
may last >24 hours
Lieberman, 2004
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Uniphasic Anaphylaxis
Treatment
Initial
Symptoms
Time
0
Antigen Exposure
Biphasic Anaphylaxis
Treatment
Initial
Symptoms
Treatment
1-8 hours
SecondPhase
Symptoms
0
Antigen
Exposure
Classic Model
Time
1-72 hours
New Evidence
Protracted Anaphylaxis
Initial
Symptoms
Time
0
Antigen
Exposure
Possibly >24 hours
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Overview of Anaphylactic Triggers
Golden. Anaphylaxis, 2004
Triggers of Anaphylaxis:
Insect Stings and Bites
• Bees
• Vespids (yellow jackets,
hornets, wasps)
• Fire ants and other ants
Less likely:
• Scorpions
• Deer & horse flies
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Iatrogenic Triggers of Anaphylaxis
• Medications
– Antibiotics
– Aspirin and other NSAIDs
– Any drug can
• Diagnostic agents
– Contrast media (IVP dyes)
• Allergen immunotherapy
• Blood transfusions
• Biological response modifiers
– Monoclonal antibodies
Joint Task Force on Practice Parameters: AAAAI, ACAAI, and JCAAI.
J Allergy Clin Immunol 2005;115:S483-523
Food-Induced Anaphylaxis
• • • • Rapid onset, multi-system, potentially fatal
Course: may be biphasic 20% of the time
Any food, highest risk: peanut and tree nuts
Risk factors for fatality:
– Delayed epinephrine
– Young adult/teenager
– Underlying asthma
– Absence of cutaneous symptoms
Emergency Management
• Prompt recognition of symptoms
• Intramuscular epinephrine
– Self-injectable device
– EpiPen Jr / Auvi Q Jr: 0.15 mg, under 50 lbs
– EpiPen / Auvi Q: 0.3 mg, over 50 lbs
• Oral antihistamines (Secondary therapy)
– Eg. diphenhydramine, 1-1.5 mg/kg/dose
• Mandatory: Emergency Dept.
• 4 hour observation period
– Potential biphasic anaphylaxis
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Treatment: Epinephrine
• Treats all symptoms of anaphylaxis and prevents
progression (antihistamines DO NOT)
• IM inject. in lateral thigh produces most rapid rise
in blood level
• Children treated w/Epi for food anaphylaxis before
ED arrival were at much lower risk for
hospitalization than if delayed until after seen in ED
• Up to 20% of time, more than one dose needed so
it is recommended to keep multiple doses
IM vs SQ Epinephrine
8 +-
2 minutes
(Epipen®)
34 -+ 14 (5 – 120)
minutes
p < 0.05
Time to Cmax after injection (minutes)
Simons: J Allergy Clin Immunol 113:838, 2004
Additional Treatment of
Anaphylaxis
• Supplemental oxygen
• Fluid replacement (10-20 cc/kg)
• H-1 antagonists (eg. Diphenhydramine)
and H-2 antagonists (eg. Ranitidine)
• Corticosteroids-but no proven benefit
• Observe for 4-24 hrs after initial
symptoms have subsided
• Severe cases: IV epinephrine,
vasopressors
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Food Allergies in Schools
• Food reactions including anaphylaxis are not
uncommon in schools
• 16% of children with a food allergy will
experience an allergic reaction in school
• Almost 25% of Peanut/nut allergic reactions
occurred in school/day care before a diagnosis
made
• A survey of anaphylaxis in school showed
epinephrine was necessary in many children
without any prior experience of food allergy
High Risk Population:
Adolescents
• They’re teenagers!
• Eat meals and snacks outside the home
• More likely not to carry their epinephrine
• Take more chances with foods…do not think
about mortality
• Keep their food allergy issues to themselves
• Are afraid to use their epinephrine autoinjector
Exercise-induced Anaphylaxis (EIA)
• Exercise alone can trigger anaphylaxis
• It is different from exercise-induced
asthma where wheezing, shortness of
breath occur in an asthmatic
• Symptoms of EIA may include itching,
hives, swelling, breathing difficulty,
dizziness, fall in blood pressure, loss of
consciousness
• It can be episodic, fatalities very rare
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Case Presentation
• 14 year old female with no significant past medical
history
• Began training for high school varsity basketball
team
• 15 minutes into practice, she developed diffuse
urticaria
• Reports eating granola bar 1 hour prior to practice;
has eaten granola bars for several years with no
reaction
• No new exposures, no new foods, no new
medications
Food-dependent Exercise-induced
Anaphylaxis (FDEIA)
• Requires food ingestion followed by exercise to
occur
• Anaphylaxis occurs when patient exercises within 2
to 4 hours of ingesting a food (wheat, celery,
shellfish have been reported)
• Severity increased with co-administration of alcohol and
NSAIDs/aspirin
• Twice as common in women, especially young
women, 60% of cases in individuals <30 years of
age
• Management: Identifying specific foods, if possible,
and avoiding exercise for 4 hrs after eating
Case Presentation
• 12 year old male with allergic rhinitis seen in clinic
for “new” food allergies
• Has year-round allergies, that noticeably worsen in
spring and are mildly worse in fall
• Reports itchy mouth and throat with fresh peaches,
cherries, and some nuts
• Symptoms worse during Springtime
• No hives, no respiratory symptoms, no GI distress
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Oral Allergy Syndrome
(Pollen-food allergy syndrome)
• Contact IgE-mediated reaction in the oropharyngeal
mucosa, onset <5 minutes
• Caused by raw fruits or vegetables, nuts, spices;
cooked foods well-tolerated
• Cross-reactive allergens in pollen and plant foods
(primary sensitization to pollen/airborne allergens
then reaction to food ingestion/plant proteins)
• Rare cases may progress to systemic reactions
Oral Allergy Syndrome
Up to Date
Oral Allergy Syndrome
Up to Date
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Oral Allergy Syndrome
Up to Date
• http://web.mail.comcast.net/service/home/
~/?
auth=co&loc=en_US&id=911241&part=2
Case Presentation
• 8 year old male with history of asthma
• Awoken at midnight with diffuse urticaria and mild
wheeze
• Recalls eating hotdog for dinner and an ice cream
sandwich for dessert around 6 pm
• Watched a movie after dinner and went to bed
immediately after
• Reports a few tick bites during summer, which took
one month to fully heal
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What is alpha-gal?
• Alpha-gal is present on the tissues and
cells of all lower mammals
• Humans and apes do not have
alpha-gal due to an inactive gene product
What is happening?
• This condition usually is associated with
bites by the Lone Star Tick
• This can result in antibodies to alpha-gal
(galactose alpha 1,3-galactose)
• When that person ingests mammalian
meat antibodies to alpha gal can cause an
allergic reaction even anaphylaxis
2009
2011
Known distribution of the tick A americanum (data from
the Centers for Disease Control and Prevention Web site).
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Skin Tes)ng Results: O1en <4mm SPT Dust
mite
Beef
Chicken
Cockroach
Lamb
Pork
Cat
Turkey
Dog
Codfish
Prick test
Intradermal
Prick test performed using lancet and intradermal testing with
25 gauge needle in the same patient on a single clinic visit.
Commins et al JACI 2009
Mammalian meat challenge sIgE to alpha-­‐gal = 29.1 IU/mL ; total IgE = 201 4hrs 25min a1er ea)ng mammalian meat: pruritus followed by ur)caria on right flank Typical History
• Reactions are delayed (~3-6 hours) after ingesting red
meat
• Angioedema or urticaria in the night can be severe
• Progressive: begins with pruritus, then urticaria, then
systemic symptoms (GI, decreased BP)
• Skin prick test responses to commercial extracts of
these meats are usualy negative
• Serum immunoassays positive to mammalian meats
(beef, pork, lamb) as is serum test for IgE to alpha-gal
• Frequently missed (and called idiopathic anaphylaxis)
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Eosinophilic Esophagitis
• Disease of esophagus triggered by foods (and
possibly environmental allergens)
• Presents with epigastric abdominal pain,
dysphagia or food impaction
• Diagnosis by endoscopy/biopsy
• Identification of food triggers using standard
allergy testing is challenging
• Treatment-topical corticosteroids, anti-reflux
medication and elimination diets
Food Allergy Diagnosis
• History
– Food ingested
– Timing of symptoms, acute reaction versus chronic disease
– Co-ingestion of aspirin, alcohol, viral infection, fever,
menstruation
– Association with exercise
-- Eczema and Asthma
• Diagnosis
– Prick skin testing
– Serum food-specific IgE
– Oral food challenges - “Gold Standard”
Diagnosis Evaluation
• Suspect IgE-mediated (allergy)
– Prick skin tests
– ImmunoCAP /RAST test (IgE levels in
blood)
• Suspect non-IgE-mediated
– Allergic gastrointestinal conditions
-- Elimination diets may be helpful
• Suspect not allergic, consider: lactose
intolerance, toxic reactions, celiac disease
(gluten-sensitivity)
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Skin Testing
• Provide rapid screening for sensitivity to allergens
• Less discomfort and cost compared to blood tests.
May need to skin test with fresh foods
• Size of skin test may be helpful in predicting
likelihood of reacting
• Negative skin tests strongly suggest the absence of
IgE-mediated allergy
Blood Tests for Foods
• ImmunoCAP/RAST test measure specific IgE
antibody levels to different foods in the blood
• Are helpful in predicting likelihood of an
allergic reaction (see cut-offs)
• High levels less likely to outgrow allergy
• Usefulness of component resolved
diagnostics
Diagnostic Decision Points
• Milk, 15 kUA/L (5 for children <2 years old)
• Egg white, 7 kUA/L (2 for children < 2 years old)
• Peanut, 14 kUA/L
• Fish, 20 kUA/L
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Limitations of Tests
• Blood test ‘screening’ not advised because may lead to
unnecessary or harmful dietary restriction which can frustrate
and confuse parents/patients
• Size of skin test and numerical value (ie. absolute # or level IVI) of the blood test do not predict severity of the clinical
reaction
• Patients can have food reactions with very low levels of
<0.35Ku/L
• So false positives and false negatives do occur so these tests
must be looked upon in the context of the history
Oral Food Challenges (OFC)
• Physician supervised
– Open
– Single-blind
– Double-blind, placebo controlled
• Negative
– Reintroduce food
• Positive
– Elimination diet
– Awareness of cross-contamination from shared equipment
Oral Food Challenges
• Decision to perform an OFC
– No recent reactions (past 6-12 months)
– No severe anaphylaxis in past 24 months
– PST/serum food IgE negative or significantly decreased
from previous evaluation
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Risk Factors for Food Allergy
• The hygiene hypothesis-cleanliness is not next
to godliness when it comes to allergy
• Low Vitamin D levels
• Delayed consumption of allergenic foods rather
than introducing at an early age
• Diagnosis of asthma-risk for severe reactions
Evidence for Vitamin D
• Higher rates of egg and peanut allergy in regions further
from the equator
• Move to someplace warm and sunny!
-Food anaphylaxis more common in northern US
• Adequate levels of vitamin D protective against food
allergy (levels <15 ng/ml vs >30 ng/ml associated w/risk
for peanut allergy)
• Maternal intake of vitamin D during pregnancy may be
associated with decrease risk
Early Exposure Hypothesis
• Peanut allergy less prevalent in countries where early
exposure is common
• Study comparing practices in Israel and the UK– peanut
allergy rare in Israel, in UK similar to US
• Oral tolerance may require early exposure and is
dependent on dose and timing
• Delayed oral exposure and elimination diets may bypass
development of oral tolerance (and result in food
allergies)
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Factors That Can Affect
Allergenicity of Foods
• Preparation: Roasting vs. boiling of
peanuts
• Chemical properties of food: Heat
stable vs. heat labile proteins (the oral
allergy syndrome)
• Gastric digestion: Can affect the
allergenicity of some food proteins
• Medications: Beta blockers, ACE
inhibitors increase anaphylaxis risk
• Alcohol consumption
Natural History
• Milk, egg, wheat, and soy allergy
– Majority resolve by school age
– But, these allergies are lasting longer
often into 2nd decade
• Peanut, tree nuts, fish, shellfish
– Usually lifelong
– 20% of young children outgrow peanut, 9% tree nuts, 7-9%
recurrence of peanut allergy (increased risk if not ingested
regularly)
Primary Prevention-Learning Early About
Peanut Allergy (LEAP)
• 640 infants aged 4-11 months of age
• 2 cohorts: negative skin test to PN and
those with small < 4 mm skin test to PN
• Consumption group fed 2 grams of PN 3
times/week, BAMBA snack food, peanut
butter
• At 5 years consumption group 80x less
likely to have a peanut allergy
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Prevention of food allergy
• LEAP Study-Early peanut introduction
significantly reduces allergy risk
• Selected population-severe eczema, egg
allergy, not/mildly sensitized to peanut
• Excluded infants already allergic to peanut
• Importance of skin testing first
• Caution in generalizing or making
recommendations for other infants/children
Food Allergy Prevention:
• No evidence for protective effect of dietary maternal
restrictions during pregnancy and lactation
• A recent study showed eating nuts during pregnancy may lead
to a lower risk for nut allergy
• For infants at high risk of atopy, exclusive breast-feeding for at
least 4 months decreases cumulative incidence of atopic
dermatitis (AD) in the first 2 years
• For high risk infants feeding with extensively hydrolyzed
formula protects from development of AD in early childhood
Food Allergy Prevention
• There is no convincing evidence for the use of soy formula for
allergy prevention
• There is no evidence that delayed introduction to solid food
beyond 4-6 months has a protective effect
• For infants older than 4-6 months, there is no sufficient data to
support a protective effect of any dietary intervention
• However, prolonged avoidance of specific allergens is not
protective and might be a risk factor with regard to food
allergy prevention
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Food Allergy Treatment
• Allergen avoidance has been the mainstay of
prevention and management
• Conventional immunotherapy (shots) many side
effects, risky, not an option for food allergies
• Periodic evaluations are recommended every 6-12
months, especially for children who mostly outgrow
food allergy
• Oral immunotherapy is efficacious and has been
shown in studies and practice to be safe and effective
Oral Immunotherapy (OIT)
• Clinical studies (milk, egg and peanut) at Duke,
University of Arkansas, Mt. Sinai, Johns Hopkins
(safe, effective therapy)
• Lancet study-Blinded-controlled study-85% of
patients could be desensitized
• Annals of Allergy study-OIT to peanut has significant
impact on quality of life
• Stanford research-Examining safety and benefit of
OIT to multiple foods at one time
Peanut Oral Immunotherapy
• New England Food Allergy Treatment Center (West
Hartford, CT)
– Desensitize patients with peanut allergy
– Fed small incremental amounts of peanut protein over
weeks and months
– To date, treated >550 patients age 4 through adulthood;
>90% patients successfully desensitized
– Goal is not to cure, but that accidental exposures does not
result in clinical symptoms
– Now treating tree nut, milk, egg allergy
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Reactions during Treatment
• Initial desensitization day (5-6 hours)
build-up phase (6-8 months) and
maintenance phase
• Reactions during build-up common, mostly
GI and can be managed with dose adjust.
• Reactions during maintenance including
anaphylaxis have occurred in 5% of pts.
• Often associated with exercise, viral or
febrile illness, hot showers, menses
OIT Results
• Highest initial IgE level to peanut associated with
slower build-up and more reactions
• Virtually all patients on maintenance pass a
peanut challenge
• Recent studies seem to indicate longer duration
of maintenance OIT may lead to tolerance
What the experts think…
• “When performed by experienced
investigators in an appropriate setting,
peanut OIT is a safe, allergen-specific
therapy effective in inducing
desensitization and providing protection
against accidental ingestion with ongoing
therapy”
Varshay P.,Jones SM, Scurlock AM, et al. J
Allergy Clin Immunol 2011;127:654-60
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Other Modalities of Treatment
• Use of heated allergens: Consuming baked milk/
egg-1-3 servings/day accelerates tolerance
• SLIT: Studies w/milk, peanut, hazelnut-efficacy
observed-not as robust as OIT
• Chinese herbal formula: FAFH-2, in human
trials-need to consume a lot of capsules/day
Other modalities (continued)
• EPIT: Epicutaneous immunotherapy (Allergy
patch-delivery of allergen to skin surface) studies
very encouraging in children
• Intralymphatic immunotherapy-injection into
lymph nodes
• Immunotherapy with modified proteins designed
to be hypoallergenic
Practice Parameters
-Relatively small amount of foods cause most food
allergies: cow’s milk, egg, soy, wheat, peanut, tree
nuts, fish, shellfish
-Risk of cross-reacting foods: walnut/pecan,
pistachio/cashew, shellfish, fish, mammalian milk
-Latex allergy and caution with bananas,
avocados, kiwi, chestnut, others
-Encourage exclusive breastfeeding for 4-6 months
-With positive family history use hydrolyzed
formula for possible prevention of atopic dermatitis
and cow’s milk allergy
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Practice Parameters (Don’t)
• Maternal allergen avoidance or avoidance of
complementary foods at weaning
• Food allergy/additive avoidance in ADD/ADHD
• General food allergy testing for chronic hives
• Asthmatics routinely avoiding sulfites
• Allergen testing for IgG, hair analysis,
provocation/neutralization, applied kinesiology
• Total serum IgE for food allergies and general
allergy blood test screening for food allergies
Summary
• Risk Factors: Low vitamin D, delayed
introduction of allergenic foods, hygiene
hypothesis
• Newly recognized condition: delayed
anaphylaxis due to alpha-gal
• Primary prevention: LEAP study, Vitamin D
supplementation, hypoallergenic formula
• Oral immunotherapy gaining more widespread
acceptance
It’s a peanut!
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Component diagnostics
• For peanut several key proteins (Ara h
1,2,3,8)
• Ara h 2 if elevated associated with more
severe reactions/anaphylaxis
• Ara h 8 (homologous to Birch pollen)
associated with milder allergy symptoms
• Milk: casein-heat stable protein, elevated
levels suggest persistence of allergy
• Egg: ovomucoid is heat-stable
Component Diagnostic Testing
• For peanut several key proteins (Ara h 1,2,3,8)
• Ara h 2 if elevated associated with more severe
reactions/anaphylaxis
• Ara h 8 (homologous to Birch pollen) associated with
milder allergy symptoms
• Peanut component panel available at commercial labs
and covered by insurance
• Emerging field-other foods being studied
Summary: alpha-gal
• Delayed reactions occurring 3-6 hours after eating
mammalian meat has been confirmed in subjects with
elevated IgE to alpha-gal
• Lack of symptoms before 3 hours suggests that there is
delayed appearance of the relevant form of particles or
molecules carrying alpha-gal into the bloodstream.
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Mammalian meat challenge Diffuse ur)caria appeared at 4hrs 15min a1er ea)ng meat (le1 arm shown here) 28