Washington State NAPNAP
2013 Spring Conference
Food Allergy Cases
March 11, 2013
David R. Naimi, DO
Clinical Assistant Professor of Pediatrics
University of Washington School of Medicine
Northwest Asthma & Allergy Center
Introduction
• Undergraduate
– Go Dawgs!
• Medical School
– (Pomona, CA)
• Pediatric Residency
– Case Western - Rainbow
Babies & Children’s
• Allergy/Immunology
Fellowship
– CHOP & U Penn
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Seattle
Redmond
Red Ridge
Issaquah
Renton
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Everett
Mt. Vernon
Yakima
Richland
Learning Objectives
• Understand the clinical manifestations of
food allergic disorders
• Appreciate the utility of tests used to
diagnose food allergy
• Understand when to refer to an allergist and
how to follow patients with food allergy
• Appreciate and respond to the educational
needs of patients diagnosed with food
allergy in regard to avoidance and treatment
Cases
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Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
Food Allergy Definitions
• Adverse food reactions – any untoward
reaction to food or food additive
– Food allergy/hypersensitivity – adverse food
reaction due to an immunologic mechanism
• Example: Peanut allergy
– Food intolerance – adverse reaction due to a
physiologic or non-immunologic mechanism
• Lactose intolerance
• Caffeine
Differences between IgE & Non-IgE food reactions
IgE mediated allergy
Symptoms
Timing of
symptoms
Examples
Non-IgE mediated
Skin, respiratory tract, GI GI tract and/or skin, other
tract, Cardiovascular
Rapid (seconds to
minutes). Rarely past
2hrs. Reproducible.
Peanut anaphylaxis
Subacute, chronic (>2hrs to
days)
-Celiac disease
-Milk-protein induced
proctocolitis
-FPIES (Food Protein
Induced Enterocolitis
Syndrome)
Mixed IgE/non-IgE: Eosinophilic Esophagitis & Atopic Dermatitis
Spectrum of Immune mediated
Food Allergy
IgE-Mediated
Mixed
Non-IgE-Mediated
Skin
- Urticaria
- Atopic
Dermatitis
- Angioedema
Respiratory (isolated symptoms rare)
- Asthma
Rhinitis
- Dermatitis
herpetiformis
Histamine related symptoms???
Gastrointestinal
- GI “Anaphylaxis”
- Oral Allergy
syndrome
Systemic
- Eosinophilic
gastrointestinal
disorders(EoE)
-Anaphylaxis
-Food-associated or
exercise-induced anaphylaxis
- Celiac disease
- Infant
gastrointestinal
disorders
Cases
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Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
The infant with “mucousy” or blood
streaked stools
• 2mo exclusively breastfed infant
• Mucousy stools w/occasional streaks of blood noted
recently
• Clinical history NOT consistent w/constipation.
• Normal growth & feeding pattern.
• Normal exam (no rectal fissures).
Questions to ask yourself
• Diagnoses?
Food protein induced proctocolitis. Major cause of colitis
<12mo. >50% of infants usually exclusively breastfed
• IgE or non-IgE mediated?
Non-IgE
• Risk of anaphylaxis?
No
• What is the most common cause?
Cow’s Milk, often Soy
• Skin or blood testing needed?
No
• What to advise parent?
Mother to trial off of Cow’s milk/dairy +/- Soy
• Is this going to improve?
Yes. Usually resolves by 9-12mo
What if this patient were bottle fed?
• Change to hydrolyzed formula (Alimentum,
Neutramigen, etc…)
• Consider elemental formula (Elecare, Neocate) but
NOT likely needed
• Consider Soy formula (however, high likelihood
of problems with soy)
– Consider soy as an alternative nutrient AFTER age 6mo per
European Society for Pediatric Gastroenterology Hepatology and
Nutrition (ESPGHAN) Recommendations
Cases
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Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
12yo with oral itching with almond,
fresh fruits & veggies
• Began 1-2 yrs ago
• Occurs w/fresh apple, pitted
fruits, melons, & fresh carrot
• Same symptoms w/almond
• No problems w/cooked fruits &
veggies
• No other symptoms (no hives,
respiratory symptoms, etc).
Oral Allergy Syndrome
(aka Pollen Food syndrome)
• Oral itching w/certain foods (mild lip angioedema
possible)
– Contact reaction in oropharyngeal mucosa
• IgE mediated
•
•
•
•
– Onset <5min
Raw fruits/veggies and some nuts
Heat Labile proteins (cooked foods well-tolerated)
Affects ~50% of adults w/allergic rhinitis
Rarely causes serious symptoms (<1% risk of
anaphylaxis) – possible increased risk w/tree nut &
peanut
Oral Allergy Syndrome
(aka Pollen Food syndrome)
• Cross-reactive allergens
– BIRCH: apple, peach, apricot, cherry, and plum,
pear, almond, hazelnut, carrot, celery, parsley,
caraway, fennel, coriander, aniseed,
– GRASS: Melon, Tomato, Orange, Lettuce, peanut
– *RAGWEED: cantaloupe, honeydew,
watermelon, zucchini, cucumber, banana
*There is NO RAGWEED in the Pacific NW
How to alleviate oral allergy
syndrome
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•
•
•
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Cook/heat food (20sec in microwave)
Avoid ripe fruits
Peel & wash
PO antihistamine few hrs before ingestion
Allergy immunotherapy (allergy shots)
Food Allergens
Type
Class I
Class II
Description
Water soluble glycoproteins Plant-derived
Examples
Wheat, Egg, Milk, Peanut
Apple, Carrot, Celery
Characteristics
Resistant to heat, acid,
and proteases
Highly heat labile. Cooking
reduces allergenicity.
Susceptible to digestion
Sensitization
GI tract
Respiratory tract w/crossreactive pollens
Clinical reaction
Anaphylaxis, eczema
Oral allergy syndrome
Cases
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Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
The infant w/eczema
• 4mo infant w/eczema - present since he was
“weeks” old – involving most areas of body.
• Birth & developmental hx normal. Growing &
feeding well w/out history of recurrent infections
or chronic diarrhea.
• Exclusively breastfed – mother asking if FOOD
ALLERGIES are playing a role in eczema certain foods she ingests possibly flares his skin
(? dairy)
The infant w/eczema
• Eczema only partially
improved w/1%
hydrocortisone regularly
• Physical exam:
– significant for scattered dry &
minimally erythematous
patches
– few excoriations on cheeks,
trunk, & extremities.
What is the relationship between eczema
and food allergy?
They CAN be associated … extent of this
association is controversial
• Potential causes of eczema
– Young children (<5yo)  Food allergy +/- Env allergens
– Older children & Adults  Env allergens
• Rate of sensitization to foods ranges
from 30-80% (varies upon population
represented)
– However … ACTUAL rate of confirmed food allergy is
LOWER
The relationship between eczema
and food allergy
• Ingestion of food flare of patient's eczema
(increased itching and redness).
– IgE: min to hrs after ingestion
– Non-IgE: hrs to days after ingestion
• If the child eats a food regularly, then
he/she may have persistent symptoms of
eczema
IgE Mediated Food Allergy
• Allergies to various seeds
(e.g. sesame) seem to be
increasing.
• Wheat, egg, and milk
sensitization more
commonly associated w/
eczema in children.
WEMPSS = Wheat, Egg,
Milk, Peanut/Treenut,
Soy, Seafood
(90% of food allergy)
Most likely  severity =
peanut, treenut, seeds,
seafood.
Children
Wheat
Egg
Milk
Peanut
Tree nuts
Soy
Finned fish
Shellfish
Adults
Peanut
Tree nuts
Finned fish
Shellfish
Raw fruits/veggies
(oral allergy syndrome)
The modern diet
“Exotic foods”
– Increased reported allergic reactions
•
•
•
•
Kiwi
Mango
Papaya
Seeds (sesame, poppy, mustard)
Too young for testing?
• Foods
– No ‘cut-off’ age for skin or blood testing to foods
– If an infant/child has NEVER been exposed to a food (inutero, breastmilk, etc) then sensitization may not be present
• Environmental allergens
– <2yo: unlikely to be sensitized to allergens outside home
– Testing to indoor allergens is still appropriate for <2yo
– However, for environmental allergens: skin testing &
blood testing (allergen specific IgE) can LAG behind
clinical symptoms
Testing: What would I do in this case?
• Skin testing - Foods
– Wheat, Egg, Milk, Peanut, Soy
– Few other foods very common in mother’s diet (ie corn,
seafood)
– Fruits/veggies not likely common causes
• Skin testing – Environmental allergens
– Dust mites
– Pets (if applicable)
• If blood testing ordered (food specific IgE): would
also obtain a total IgE
What NOT to do when testing for food
allergy
• Skin/blood testing should NOT replace taking a hx
• Do NOT blindly order “food allergy panels” (This is
likely to yield clinically irrelevant results & FALSE food allergy dx)
– Problem: some labs charge less for “panels.”
A possible exception to the above statement …
• Younger children w/recalcitrant eczema
– Obtaining a history of food association may be difficult
– One of the FEW times I consider “screening” for food
allergy. More appropriate for children <5yo
Skin Testing or Blood Testing?
Food Allergy Testing:
Identifying the presence of allergen specific IgE
Skin Prick Testing
Food Specific IgE (ie immunocap or
radioallergosorbent tests)
Cost effective
More expensive
Quick (results in 15min)
Wait days for lab results
Generally less painful
More painful
Affected by po antihistamines
NOT affected by po antihistamines
Difficult to perform if skin area is flared
or if dermatographic. Limited by space.
Not affected by active dermatitis nor
dermatographia
Generally avoid in pregnancy (despite
its relative safety)
Preferred during pregnancy
Generally more helpful for determining
the absence of sensitization (>95%
negative predictive value)
Generally more helpful for determining the
likelihood of a clinical reaction (positive
predictive value)
High sensitivity (90%) esp fresh foods
Sensitivity varies among different foods
Moderate specificity (50-95%:
depending on food & patient’s clinical
history)
Moderate specificity
Skin testing: Epicutaneous
Skin testing - Interpretation
 Measurements of wheal & flare, use
histamine/saline controls
 Prick test: >3mm wheal w/10mm flare
 Read @ 15 min
 Oral antihistamines, not steroids,
produce false (-) tests and alter the
results of skin testing
 “Other” antihistamines = Ranitidine,
Famotidine, Tricyclic antidepressants
Results of testing
in this case
• Egg & Milk IgE quite elevated
– Egg = 7 kU/L
(normal <0.35)
– Milk = 10 kU/L (normal <0.35)
• Food specific IgE negative (<0.35 kU/L) for
all other allergens
• Total IgE minimally elevated
Sampson HA. Food and Drug Reactions and Anaphylaxis: Utility of food-specific IgE concentrations in
predicting symptomatic food allergy. J Allergy Clin Immunol 2001; 107(5): 891-896.
Diagnostic Decision Points for
Food Specific IgE
Food
Cow’s Milk
Egg White
Peanut
Tree nut
Fish
Serum IgE (kU/L)
~95% Fail
~50% Fail
15
2
5 (if less than 2yo)
7
2
2 (if less than 2yo)
14
2 (Hx +)
5 (Hx -)
15
--20
---
Sampson HA. J Allergy Clin Immunol 2001; 107(5): 891-896.
What do you do w/the results?
• Demonstration of sensitization (via skin or
blood test) to a food does NOT mean that the
patient has clinical reactivity to that food
(+) Test ≠ Clinical Relevance
Food Allergy
Diagnoses
• Clinical reactivity can be confirmed
by oral food challenges OR food
elimination diets.
• Double-blind, placebo-controlled
food challenge (DBPCFC)
– “gold standard” … but not practical.
• Open food challenges performed
more often in the allergy clinic
– more practical.
What next?
• Maternal elimination of egg & milk from
diet. Up to 2 wks is often enough time to
determine improvement of eczema.
• Refer to allergist, especially before
introduction of solid foods
– AVOID unnecessary food avoidance! This could
cause increased sensitization too food.
“Will my baby grow out of his
allergies?”
Natural history of Food Allergy
Food
When to expect resolution of IgE mediated allergy
Wheat
Resolves in 80% of patients by school age
Egg
Majority will outgrow by school age (~65%)
Milk
Majority will outgrow by school age (~80%)
Peanut/
Tree nut
Peanut: resolves in 20-25%, Tree nut: resolves in ~9%.
Peanut: 7-10% recurrence of allergy may occur if a food
challenge is passed & patient doesn’t eat the food
regularly after this.
Soy
Generally outgrown more quickly than Egg or Milk. Often
(+) if have concurrent peanut allergy [both are legumes].
Fish/Shellfish
Less likely to resolve. Adult onset is more common.
Limited data.
Food allergies to most foods, other than fish/shellfish &
peanut/treenuts, are usually outgrown
Following a child w/food allergy
• Food allergic children should be monitored
regularly by a pediatrician & allergist.
• Serial testing (skin test and/or serum IgE) usually
done yearly (depending on type of food & age of
patient).
• If clinical history & lab testing is reassuring, then
an oral food challenge can be performed in
controlled setting to ensure resolution of food
allergy.
Following a child w/food allergy
• Elevated initial food allergen specific IgE is assoc
w/lower rate of resolution
• Resolution of Atopic Derm may be a useful marker
for onset of tolerance
• Negative tests (skin or blood test) DO NOT
guarantee loss of allergy.
• IgE antibodies to a specific food can PERSIST even
after clinical reactivity to that food has cleared.
– Therefore, oral food challenges (often done by allergists in
the office) can be helpful.
CLINICAL HISTORY
Skin Testing
Food specific IgE
Food Allergy Diagnoses
Standard of Care for Food Allergy
•
Every food allergic reaction has possibility of
developing into life-threatening reaction
•
•
may depend upon how much of the food is eaten
Long-standing principle = complete avoidance of
even minute exposures and ready access to
self-injectable epinephrine.
Recent data has challenged the
long-standing idea of strict
avoidance, instead, attempting
to incorporate small amounts of
the food into the diet.
Effect of Cooking &
Digestion on Food Proteins
M
I
M
I
L
1
K
M
I
L
L
K
K
Processing
K
L
2
Children with milk (and egg) allergy MAY often tolerate
baked-milk or baked-egg products
M
I
BAKED GOODS
Changing the Paradigm: from Strict
Avoidance to a Limited Diet
• 70% of children with egg allergy tolerate in
baked goods
• 75% of children with milk allergy tolerate in
baked goods
• Regular ingestion of these proteins is
associated w/decreasing skin test size &
milk/egg specific IgE
• ? may result in development of tolerance
What about future vaccines?
Egg Allergy & Vaccines:
Vaccines that contain “significant” amounts of
Egg protein:
• Influenza
• Yellow Fever
MMR IS OK!!!
Egg allergy & Influenza Vaccination
• Studies involve TIV, not
intranasal LAIV (TIV = Trivalent
Influenza Vaccine. LAIV = Live Attenuated
Influenza Vaccine … “FluMist”)
• Vaccine administered by
provider familiar w/potential
manifestations of egg allergy
• Administer in setting
w/emergency equip available
• Observe x 30min or more
• Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines:
recommendations of the Advisory Committee on Immunization Practices (ACIP)--United States, 2012-13 influenza
season. MMWR Morb Mortal Wkly Rep. 2012 Aug 17;61(32):613-8.
• Greenhawt MJ, et al. Safe administration of the seasonal trivalent influenza vaccine to children with severe egg
allergy. Ann Allergy Asthma Immunol. 2012 Dec;109(6):426-30.
What should you tell the mother about the
introduction of future foods for her infant?
• Previous recommendations for delaying intro of solid
foods for purpose of preventing allergic disease in
“HIGH RISK” infants is NOT EFFECTIVE
• Previous AAP recommendations = delay introduction
of certain highly allergenic foods in high risk children:
– cow's milk until age ……………………. 12mo
– eggs until age …………………………... 24mo
– peanuts, tree nuts, fish, and shellfish … 36mo
What should you tell the mother about the
introduction of future foods for her infant?
• New recommendations:
– insufficient evidence to recommend any specific practices
concerning intro of foods after 4-6 mo for prevention of
allergic disease in *“high risk” infants.
– Breastfeeding is best for ≥4mo. If NOT breastfed,
hydrolyzed formulas MIGHT be helpful in “high risk”
infants to delay or prevent atopy.
– DO NOT delay introduction of solid foods for “high risk”
infants. This practice might increase the risk of allergy.
*”High risk” definition: having at least one 1st degree relative (parent or sibling)
w/documented allergic condition (mod/severe atopic dermatitis, food allergy,
asthma).
Greer et al. Pediatrics 2008; 121:183.
What should you tell the mother about the
introduction of future foods for her infant?
• General guidelines for introducing solid foods to an
infant's diet are also appropriate for infants at “high risk”
for allergic disease.
• Some reasons to REFER to an allergist:
- Breastfed infant develops atopic dermatitis before
solid foods are introduced or has an allergic reaction
during/after breastfeeding.
- Infant develops allergy to a food or shows signs of
allergic disease.
Cases
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Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
Sarah & the Cashew cookie
• Age 17
• Ate a “cashew” cookie and developed
anaphylaxis  treated in the emergency
department
• History indicates she regularly tolerates cashews,
pistachio, almonds, walnuts, pecan and peanuts
Which is the next most appropriate course of
action?
A) Advise to avoid all tree nuts
B) Advise to avoid cashew
C) Perform allergy tests to cashew
D) Determine the ingredients of the cookie
Sarah & the Cashew cookie
• Age 17
• Ate a “cashew” cookie and developed
anaphylaxis  treated in the emergency
department
• History indicates she regularly tolerates cashews,
pistachio, almonds, walnuts, pecan and peanuts
Which is the next most appropriate course of
action?
A) Advise to avoid all tree nuts
B) Advise to avoid cashew
C) Perform allergy tests to cashew
D) Determine the ingredients of the cookie
Diagnosis Requires Careful History
• The cookie package indicated that
macadamia nuts were an ingredient
• Sarah had been eating cashews
but infrequently (once/twice) ate
macadamia nuts
• Allergy tests (+) to macadamia &
negative to cashew
• Instructions could include:
– avoidance of all tree nut products or …
– continue ingestion of tolerated nuts
when certain that macadamia is not
included
General questions to ask a patient
w/suspected food allergy
•
•
•
•
•
•
History, History, History!
What food? How much?
What was the reaction?
Timing of symptoms?
Reproducible?
Any ingestions after reaction?
– Can develop allergy … (esp seafood)
Cases
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•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
Stephanie vs the Bagel
•
•
•
•
14 years old, has asthma
Sesame allergy (known)
Ate a bagel with no visible sesame
Has no hives, develops repetitive coughing, hoarse
throat, trouble swallowing, vomiting
What treatment is most appropriate?
A) Antihistamine
B) Injected epinephrine
C) Asthma inhaler
D) Heimlich maneuver
Anaphylaxis May Occur Without
Hives
What treatment is most appropriate?
A) Antihistamine
B) Injected epinephrine
C) Asthma inhaler
D) Heimlich maneuver
Treatment of Food Allergy
• Avoid offending food! If in doubt, don’t
eat it!
• Read food labels!
• Early use of epinephrine!!
• Written plan for emergencies.
• Wear Medic-alert bracelet.
• Ensure nutritional needs are being met.
Food-induced Anaphylaxis
•
•
•
•
Frequency: ~150-200 deaths/ year
Food allergy #1 cause of anaphylaxis in ER
Rapid onset, up to 30% biphasic
Risk factors for fatal, food-induced
anaphylaxis
–
–
–
–
Major risk factor: delayed use of epinephrine
High risk groups: teenagers/young adults
High risk co-morbidity: asthma
Confusing physical symptom: urticaria may be
absent in up to 10% of cases
Cases
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•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
15yo w/fatigue, h/a, occasional abd
pain and loose stools
• Questionable cause
• Workup & labs normal thus far
• “Dairy” and “wheat” might be
the cause, but unclear
• If this is food related, seems
delayed (>2-3hrs) and not
immediate
So … is this most likely an
“Intolerance” or “Allergy”
?
… my neighbor recommended a
food allergy/sensitivity panel …
• Obtained blood test at local “allergy lab.”
• (+) to various foods: grains, dairy, egg,
blueberry, etc…
• Blood test report = IgG testing
IgG to foods
• Proposed to identify nonIgE-mediated
hypersensitivity to foods:
IBS, migraine headaches,
myalgia, fatigue, etc
• Assays may measure
total IgG, IgG subclasses
(i.e. IgG4), or IgG/IgE
combined testing.
www.usbiotek.com
IgG to Foods: Availability
• Large scale screening for hundreds of food
items by ELISA-type and RAST-type assays
• USA & several European countries,
‘mainstream’ allergy diagnostic labs now offer
IgG assays to foods
• Direct-to-consumer advertising for panels of IgG
• Direct marketing by some companies to PCPs
• May not be covered by a patient’s medical
insurance
What I tell my patients
• Food intolerance vs True allergy
• Food intolerance is a TRUE entity, but there is NOT an
accurate way to actually “test” for this
• IgG testing is controversial and is/should be used for research
purposes.
What I tell my patients (cont..)
• IgG is elevated to many foods in healthy individuals & is often
(+) to what is common in our diet: (Wheat/Gluten, Dairy, and Egg).
– Patients who note improvement w/avoidance of IgG (+) foods often
DRASTICALLY change their dietary habits
• If food intolerance/sensitivity is suspected:
– Best way to diagnose this is avoidance of above foods/food groups for a certain
duration (few/several weeks) followed by re-introduction
– Consultation with dietitian if continued avoidance of foods is done
(2004) - UK
(2005) - UK
(2006) - USA
(2007) - China
(2007) - China
Zar et al
25 IBS
(2005) – UK
(13 IBS-D, 10 IBS-C,
2 alternating)
IgG4
6mo elimination
IgG4 antibodies to milk, eggs, wheat, beef, pork and lamb were elevated.
Significant improvement reported in pain severity (pB/0.001), pain
frequency (p/0.034), bloating severity (p/0.001), satisfaction with bowel
habits (p/0.004) and effect of IBS on life in general (p/0.008) at 3mo
& 6mo. Rectal compliance was significantly increased (p/0.011) at 6mo.
Critiques
To be discussed
(2004) - UK
Considerable overlap observed in IgG titers for
certain foods between IBS and controls. IBS pts:
elevated IgG4 abs to ave of 8 foods. Controls: 5
foods. No correlation seen between pattern of
elevated IgG4 ab titers & patients’ symptoms.
(2005) - UK
No placebo group. Probiotics were also given.
Potential for placebo effect was huge. Authors discuss
the detection of serum IgG antigen-ab complexes, so
what was actually measured is not clear.
(2006) - USA
(Chinese). No Placebo diet group.
(2007) - China
No significant correlation between symptom severity and
elevated serum food antigen-specific IgG Abs.
(2007) - China
Zar et al
25 IBS
(2005) – UK
(13 IBS-D, 10 IBS-C,
2 alternating)
Noantibodies
placebo to
diet
group
difficult
to further
IgG4
milk,
eggs,(thus,
wheat,
beef, pork
and lamb were ele
IgG4
interpret
these
data,
b/c
potential
for
placebo
effect). pain
Significant improvement reported in pain severity (pB/0.001),
6mo elimination Data at 6mo only available on 15 patients. Patients
frequency
(p/0.034),
bloating
severity
(p/0.001),
satisfaction
eliminated
average
of 8 foods
(most
common
being with b
habits
(p/0.004)
andin
effect
of IBS diet)
on lifeincluding
in generalmilk,
(p/0.008) at 3m
foods
common
a Western
& 6mo.
compliance
significantly increased (p/0.011) a
eggs,Rectal
beef, pork,
wheatwas
& tomatoes
Results of studies of IgG antibody elimination diets for migraine
headaches
Author
Subjec
ts
Trial
Results
Alpay K, et al
30
migraine
Double blinded
randomized
controlled
cross-over trial
6wk
elimination
Average count of reactions with abnormally high
titer was 24±11 against 266 foods. Compared to
baseline, there was statistically significant
reduction in # of headache days (from 10.54.4 to
7.53.7; P<0.001) and # of migraine attacks (from
9.04.4 to 6.23.8; P<0.001) in the elimination diet
period.
true diet
(n = 84)
sham diet
(n = 83)
Single blind
two arm
Randomized
controlled trial.
true diet vs
sham diet
12wk
elimination
Elimination
diet
Small decrease in # of migraine like headaches over 12
wks, although this difference was not statistically
significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18).
At 4 wks, use of the ELISA test with diet elimination
advice significantly reduced # of migraine like
headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04).
Disability and impact on daily life of migraines were
not significantly different between the true & sham
diet groups.
Statistically significant differences in the number of
positives for IgG food allergens between patients with
migraine and a controlled group.
Elimination diets successfully control the migraine
without the need of medications.
Cephalalgia
2010
Turkey
Mitchell N, et al
Nutrition Journal
2011
UK
Arroyave H, et al
Revista Alergia
Mex
2007
Mexico
56
migraine
56
controls
Results of studies of IgG antibody elimination diets for migraine
headaches
Author
Alpay K, et al
Cephalalgia
2010
Turkey
Mitchell N, et al
Nutrition Journal
2011
UK
Subjec
ts
30
migraine
Double blinded
randomized
controlled
cross-over trial
6wk
elimination
true diet Single blind
two arm
(n = 84)
sham diet Randomized
controlled trial.
(n = 83)
true diet vs
sham diet
12wk
elimination
56
Arroyave H, et al
migraine
Revista Alergia Mex 56
2007
controls
Mexico
Trial
Elimination
diet
Critiques
Low number of patients
Relatively short follow-up
Potential carry-over effect of a cross-over design
Recruited participants who self-reported their
migraines (their headaches may not have been from
migraines)
Small decrease in # of migraine like headaches over
12 wks, although this difference was not
statistically significant (due to diet adherence?)
Disability and impact on daily life of migraines
were not significantly different between the true &
sham diet groups.
No Placebo group
Not blinded
• Double blind, randomized, controlled, parallel design
• 150 outpatients w/IBS randomized to receive, for 3mo, either a
“true diet” excluding all foods to which they had raised IgG
antibodies (ELISA) or a “sham diet” excluding the same
number of foods but NOT those to which they had antibodies.
• Primary outcome measures = change in IBS symptom severity
& global rating scores. Secondary outcome measures =
Noncolonic symptomatology, QOL, and anxiety/depression.
Baseline demographic/clinical characteristics of the two groups, including the use of
concomitant medication, were found to be similar with the exception of IBS symptom
severity score which was slightly higher in the treatment group. 30% of patients found
to be atopic.
• Obtained IgG abs specific to
29 different food antigens.
• Most patients found to be
(+) to 6–7 foods (range 1–
19).
• Sham diet eliminated same #
of foods but not those
particular foods in the True
diet.
• Adherence was lower in
those on the true diet (24
patients withdrew from the
study in the true diet group
mainly b/c of difficulty in
following the diet)
Atkinson W, et al. Gut. 2004.
Results: Atkinson W, et al. Gut. 2004
Discussion (Atkinson W, et al. Gut. 2004.)
• Content of food elimination diets in true & sham groups were
NOT similar. Dietary restrictions in one group are NOT
controlled for by the other group.
– Treatment group excluded significantly different foods to the
control group, particularly those foods which appear to
exacerbate symptoms of IBS.
– ‘‘True diet’’: 84% avoided milk products, 49% avoided wheat
(both foods are known to be common offenders in IBS).
Total number of foods avoided by this group = 498.
– ‘‘Sham diet’’: 1.3% avoided milk, 8% avoided wheat. Total
number of foods avoided = 453.
– These differences between the diets could explain the modest
difference in outcome between the two diet groups.
– More care needs to be taken to match diets not just for number of
food types excluded but also for types of food.
Discussion (Atkinson W, et al. Gut. 2004.)
• Effectiveness of blinding is questionable.
• Does the test add specificity?
– Would patients w/IBS gain as much symptomatic
improvement if recommended to exclude the top four
foods (yeast, milk, whole egg, and wheat) compared
with an IgG antibody test based diet?
• 86.7% in treatment group avoided yeast.
– ‘‘Yeast exclusion’’ diet is not a recognized diet in
standard textbooks of diet & nutrition. This diet may
sometimes entail exclusion of a VERY wide range of
foods (i.e. bakery products, alcoholic beverages,
commercial fruit juices, cereals, condiments, dairy
produce, fungi, meat products, canned food, dried fruit,
etc).
Discussion (Atkinson W, et al. Gut. 2004.)
“Despite the inconclusive results of this study, it has regrettably
already been the subject of a press release and other publicity
by the company that provided the IgG testing for this study, in
order to promote IgG tests to the general public. On the
company’s website, IgG testing is now described as
‘‘clinically proven’’ by the British Allergy Foundation on the
basis of this study (The UK YorkTest website:
www.yorktest.com). This blurring of the boundaries between
what should be a disinterested scientific enquiry and the
promotion of a commercial venture is regrettable.”
~Dr J O Hunter
Addenbrookes Hospital
Cambridge, UK
Conclusions from the IBS studies
IBS
• May indeed be true, proven benefits from dietary change
• Trials that appropriately blind interventions in irritable
bowel syndrome are difficult to design and implement.
• IgG to the food may reflect foods commonly consumed
rather than those contributing to symptoms.
• There may be other food specific immune effects, immune
dysregulation, peptide effects or effects of dietary
components on gut microflora composition, irrespective of
IgG values.
What we do know: IgG4 & the Development of
Clinical Tolerance in OIT and SLIT Trials
Keet CA, et al. The safety and efficacy of sublingual
and oral immunotherapy for milk allergy. JACI.
2011 Nov 28.
• 30 subjects with CM allergy. After therapy, 1 of 10 subjects in
the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and
8 of 10 subjects in the OITA group passed the 8-g challenge
(P = .002, SLIT vs OIT).
• By the end of therapy, titrated CM skin prick test results and
CD63 and CD203c expression decreased and CM-specific
IgG(4) levels increased in all groups, whereas CM-specific
IgE and spontaneous histamine release values decreased in
only the OIT group.
What we do know: IgG4 & the Development of
Clinical Tolerance in OIT and SLIT Trials
Enrique E, et al. Sublingual immunotherapy for hazelnut food
allergy: a randomized, double-blind, placebo-controlled study
with a standardized hazelnut extract. JACI. 2005; 116:107–109.
• SLIT w/hazelnut. 23 patients, half randomized to active treatment
and half to placebo. 50% of those on active treatment were able to
tolerate 20 g of hazelnut at the end of the trial and showed increases
in hazelnut-specfic IgG4.
Buchanan AD, et al. Egg oral immunotherapy in nonanaphylactic
children with egg allergy. JACI. 2007; 119:199–205
• Egg oral immunotherapy in seven children with IgE-mediated egg
allergy, all of whom improved during the course of the study. Two
were able to reach a state of complete oral tolerance. Hen’s eggspecific IgG rose significantly in these subjects, IgE did not.
What we also know: IgG is increased in healthy
controls
Stapel SO, et al. Testing for IgG4 against foods
is not recommended as a diagnostic tool: EAACI task
force report. Allergy. 2008; 63:793–6.
• 13 healthy lab workers. IgG4
and IgE obtained to specific
foods
• Positive results for IgG4 against
different foods found in all
samples, and did not significantly
coincide with positive IgE.
• Increased IgG4 results were, in
none of the subjects, related to
clinical problems by intake of
foods
• “Positive IgG4 tests to foods
therefore do not indicate the
presence of food allergy, but are
probably reflecting prolonged
exposure to food components.”
(+) IgG … then what?
• Some companies construct a ‘rotary diet’ for the patient
to follow at home, though most laboratories do not get
involved in the practice of medicine in this way.
• Such dietary prescriptions can be hard to follow & may
cause nutritional deficiencies especially in children
With ANY type of testing….
• Allergy tests (SPT, serum IgE, patch testing, etc) MUST be interpreted in
the context of the patient's specific clinical history, and the diagnosis of
an allergic disorder CANNOT be based solely on a laboratory result.
• Food Allergy: Accurate diagnoses VERY important - to prevent
unnecessary avoidance of foods & potentially harmful diets
Portnoy JM. Mo Med. 2011
Testing in General: Can be a “Dangerous
Weapon”
• All Physicians must educate themselves & their
patients about the clinical utility of ANY test.
• The “Danger” = misdiagnoses, unnecessary
specialist consults, wasted time and $$$.
• Panels for food allergy may be seen by some
patients & physicians as a substitute for a
thorough history & physical exam
• Nonselective use of large panels of allergens can
lead to false positives and misinterpretation of the
results, particularly in food allergy
We need to utilize our testing wisely & responsibly
It Can be Frustrating
nightshadejournal.com
yankeegunnuts.com
Many patients w/suspected food intolerance/sensitivity are disappointed
by the negative results of IgE testing … they often look elsewhere for
testing that might be “more in line” with their expectations.
Stapel et al. Allergy. 2008.
What NOT to Say
You don’t have a
food allergy…Don’t
do ANYTHING. That
testing is hogwash.
I have a food
allergy… Look at
these IgG test
results! What should
I do?
www.onpublicspeaking.com
A More Appropriate Response
Ok … lets talk about
your symptoms &
why you think they’re
food related …
… then lets discuss
what these IgG
results mean & what
we know about IgG
testing …
www.onpublicspeaking.com
Final Thoughts
• Have an open mind & healthy skepticism
• IgG to foods needs further research.
– Too early to encourage patients or insurers to spend $$ on
panels that are suited for research, not clinical, applications
– IgG4 could be a sign of clinical tolerance, normal response to
food, or prolonged food exposure.
– IgG4 elevated in IBS, migraines, and inflammation???
• IgG to foods is “NOT ready for prime time.”
Stapel et al. Allergy. 2008.
Teuber & Beyer. Curr Opin Allergy & Clin Imm. 2007
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
12yo with allergy to salmon
• 2 ingestions
• Both ingestions reaction = skin pruritis, few
hives on abdomen  resolved with
benadryl
• Parents do NOT have Epi Pen … “he only
gets a few hives and it goes away with
Benadryl…”
Food Allergy Myth: Prior Episodes
Predict Future Reactions
• No predictable pattern
• Severity depends upon:
– Sensitivity of the individual
– Dose of the allergen
– Other factors (food matrix, exercise, concurrent
medications, airway hyper-responsiveness, etc)
• Must always be prepared for emergency
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
3yo w/hives after peanut ingestion
• Occurred immediately (within 15min) after
ingesting ½ tsp of peanut butter.
• One episode of emesis 20min after
ingestion
• No prior peanut or peanut butter ingestions
• He has not had peanut since
Results of testing
• Your colleague sent off a PANEL of food allergy
tests
• Blood testing results:
– Peanut: elevated (>50 kU/L)
– Also (+) SOY & slightly to blueberry & carrot.
• Why is soy (+)? Soy is also a legume
• Why are Blueberry and Carrot elevated? Who
knows … (carrot = pollen cross reactivity)
Sicherer S. J Allergy Clin Immunol 2001; 108:881
Cross-reactivity
Between
Foods
Mother asks: “how SEVERE is his
peanut allergy?”
Serum IgE LEVEL or skin prick test SIZE is
NOT a predictor of severity but rather the
likelihood of a reaction.
Diagnostic Decision Points for
Food Specific IgE
Food
Cow’s Milk
Egg White
Peanut
Tree nut
Fish
Serum IgE (kU/L)
~95% Fail
~50% fail
15
2
5 (if less than 2yo)
7
2
2 (if less than 2yo)
14
2 (Hx +)
5 (Hx -)
15
--20
---
What to tell family (+ tests to
peanut, soy, carrot, blueberry)
• Do NOT eat anymore peanut? Yes (do NOT)
• Stop eating soy? Peanut is a LEGUME. Most (>90%) of
legumes are actually tolerated by those with peanut allergy, even
though about 50% show a (+) IgE via serum or skin test to other
legumes.
• What question to ask: has he eaten soy, blueberry,
or carrot in the past and since this reaction?
– He has eaten ALL of these since this peanut ingestion
without problems (even tofu)
– Soy lecithin or small amounts of soybean oil do NOT
count as significant soy ingestion
CURVE BALL: What if the
testing to peanut was
negative in THIS case?
• Ok to eat peanut?
• Repeat peanut testing? When to repeat?
• Skin testing? Fresh food skin testing?
Negative tests (skin or blood test) DO NOT
guarantee lack of allergy, especially if
clinical history suggests allergy
CLINICAL HISTORY
Skin Testing
Food specific IgE
Food Allergy Diagnoses
PEANUT allergy
factoids
•
•
•
•
•
Not a true “nut”; member of legume family.
1.5 million Americans have peanut allergy.
95% of peanut allergic patients may eat legumes.
15-20% of children may outgrow peanut allergy.
Cold-pressed peanut oil – contains protein
More Peanut Allergy
Factoids
• If a child has peanut allergy, their sibling has a 7%
chance of having peanut allergy. Siblings should be
tested before peanut allergy is introduced.
• Although peanut and Tree nut do NOT cross-react,
about 25-50% of those with peanut allergy also have
tree nut allergy.
• Reactions to peanut allergy usually occur with ~1
kernel of peanut. Reactions can occur with trace
amounts (0.1-10mg).
• Prevalence of peanut allergy has doubled in the past
decade (current prevalence is ~1%)
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
55yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
Crustacean Allergy
• 21 y/o w/anaphylaxis to shrimp at ages 5yo
and 16yo.
• Doctors told his family he was allergic to
iodine in seafood
• Has been avoiding seafood.
• Food specific IgE (i.e. RAST) to shrimp >100;
Skin test 12/35 w/f
IgE towards Protein in Food NOT Iodine
Crustacean Allergy
A Medical Myth Exposed
Question: Does this patient
have to worry about iodine
or radiocontrast?
Answer: NO. There is no
relationship between
shellfish allergy and
allergy to contrast
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
2yo old with facial rash
• Child presents w/occasional
erythema on her face
w/various foods, but unable to
pinpoint which foods.
• She is otherwise well without
other symptoms after food
ingestion
• PMHx/Birth Hx uneventful
except for a h/o forcepts
delivery
Diagnoses?
Auriculotemporal syndrome
(Frey’s syndrome):
• Non-Immune Mediated Adverse Food Reaction
• A masquerader of food allergy
• Transient uni or bilateral facial flushing or sweating
following ingestion of spicy or flavorful foods.
• Infants/children w/history of forceps delivery &
damage to auriculotemporal nerve.
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
17yo who couldn’t swallow his pill
• Took an allergy pill but “didn’t go all the way
down.”
• Presented the to ER
Allegra D
Next step…
• History of prior dysphagia, but this was first
time needing ED visit
• Placed on Prevacid
• Despite good adherence on Prevacid for
several weeks  still w/intermittent
symptoms of dysphagia
• Scheduled for endoscopy & biopsy
Endoscopic findings
• Endoscopy 60
eosinophils/hpf
in esophagus
Gastrointestinal Eosinophils
Normal values, per 400x
microscopic field:
•
•
•
•
Duodenum (20)
Colon (10-20)
Gastric antrum (10)
Esophagus (0)
> 98% reported Eosinophilic Gastroenteritis (EG) cases involve antrum and/or
duodenum
Eosinophils in the Esophagus
• Reflux?
– Biopsy done while on PPI trial (at least 2mo)
– Less likely to see >20 eos/hpf in GERD
• Diagnoses = Eosinophilic Esophagitis (EoE)
Eosinophilic Esophagitis
Endoscopic findings in EoE
Biopsy is KEY to diagnoses
Normal (32%)
Furrows
(41%)
Rings (12%)
White plaques
(15%)
Eosinophilic Esophagitis - Histology
Superficial Layering
Severe Eosinophilia
Eosinophilic Microabscess
Definition of EoE
• Persistent symptoms on a PPI (adherent to therapy)
• Endoscopy is performed 4-8wks after initiation of PPI,
and biopsy reveals >15 eos/hpf in esophagus
• Approximately 5 to 10% of pediatric patients and 6%
of adult patients with poorly controlled GERD are
thought to have EE
• Chronic condition
Clinical presentation
• Clinical presentation varies per age
– Infants/younger children
• Feeding dysfunction, vomiting,
abdominal pain, FTT
– Adolescents & adults
• Dysphagia, food impaction, chest pain,
GERD symptoms (refractory).
Eosinophilic esophagitis
• Gastroesophageal Reflux
– Heartburn more likely
Dysphagia more likely
– pH probe
pH probe
• Abnormal
• Normal
– Acid blockade
Acid blockade
• Responsive
• Generally Unresponsive
– 1-5 eos/HPF
>15 eos/HPF
• Eosinophilic Esophagitis
–
–
–
–
– Male > Female
– Esophageal morphological
abnormalities (such as rings,
furrows, or exudates)
Differential diagnosis
•
•
•
•
•
GERD
Eosinophilic gastroenteritis
Crohn’s disease; inflammatory bowel disease
Medications
Infection
– Viral
– Candidal
– Parasitic
• Hypereosinophilic syndrome
Spectrum of Immune mediated
Food Allergy
IgE-Mediated
Mixed
Non-IgE-Mediated
Skin
- Urticaria
- Atopic
Dermatitis
- Angioedema
Respiratory (isolated symptoms rare)
- Asthma
Rhinitis
- Dermatitis
herpetiformis
Histamine related symptoms???
Gastrointestinal
- GI “Anaphylaxis”
- Oral Allergy
syndrome
Systemic
- Eosinophilic
gastrointestinal
disorders(EoE)
-Anaphylaxis
-Food-associated or
exercise-induced anaphylaxis
- Celiac disease
- Infant
gastrointestinal
disorders
EoE and atopy
• Strong association of EoE w/allergies
• Allergy testing may help w/management of
concomitant atopic disease
Food allergy in EoE: IgE and non-IgE
mechanism
• Children w/EoE
– Food likely a factor in many children w/EoE. Information gained
from allergy testing may help guide therapy.
– Often improve on elemental diet
• Adults w/EoE
– Less likely food allergy
– Dietary therapy sometimes used in motivated adults.
• How do we determine which food?
– Skin prick testing (IgE mediated)
– Patch testing (non-IgE mediated)
– Food elimination
• Most common foods (milk, wheat, egg, soy)
Example of Patch Testing
Treatment
• Why treat?
– Strictures
– Hiatal hernia
– No evidence of increased cancer risk
• Therapeutic options
–
–
–
–
–
–
Dietary avoidance
Medications (po steroids, topical “swallowed” steroids)
PPIs
Montelukast (questionable benefit)
Anti-IL5 (experimental)
Dilation (strictures)
Take home message
• Eosinophilic esophagitis should be
considered in …
• Adolescent & adults with:
– history of food impaction
– persistent dysphagia
– GERD that fails to respond to medical therapy
• Children with:
– Recurrent vomiting, abdominal pain, refractory
GERD
Cases
•
•
•
•
•
•
•
•
•
•
•
•
Infant w/“mucousy”/blood streaked stools
Teenager with oral itching to certain foods
Infant with eczema
Sarah and the Cashew Cookie
Stephanie vs the Bagel
15yo w/fatigue, h/a, occasional abd pain and loose stools
12yo w/salmon allergy
3yo w/hives after peanut ingestion
Crustacean allergy
2yo w/facial rash after food ingestion
17yo who couldn’t swallow his pill
Infant w/delayed vomiting after solid food introduction
Infant w/delayed vomiting after solid
food introduction
• Baby J: 20 wk old, former FT infant, exclusively
breast-fed
• 16 wks  small amts rice cereal tolerated
• 17 wks  few bites of apple introduced
• 18 wks  larger amts rice cereal & apples
– 1.5-2h later: nonbilious emesis (2hrs dry-heaving)
– Limp, brought to ED
– Admitted: heme (+) stools, normal head CT, KUB & barium
enema
– Diagnosed w/apple allergy & EpiPen prescribed
Additional history…
• Next few days, he did well exclusively breast-fed
• Day before admission, he was given a spoonful of
rice cereal. 2hrs later developed emesis (nonbilious,
repetitive).
• In ED, limp and ill-appearing.
• Afebrile, HR 157 bpm, BP 63/45.
• Treatment: subcutaneous epinephrine without
improvement and IVF
• Negative sepsis workup; determined to have…?
Spectrum of Immune mediated
Food Allergy
IgE-Mediated
Mixed
Non-IgE-Mediated
Skin
- Urticaria
- Atopic
Dermatitis
- Angioedema
Respiratory (isolated symptoms rare)
- Asthma
Rhinitis
- Dermatitis
herpetiformis
Histamine related symptoms???
Gastrointestinal
- GI “Anaphylaxis”
- Oral Allergy
syndrome
Systemic
- Eosinophilic
gastrointestinal
disorders(EoE)
-Anaphylaxis
-Food-associated or
exercise-induced anaphylaxis
- Celiac disease
- Infant
gastrointestinal
disorders
FPIES: Food Protein Induced
Enterocolitis Syndrome
• Onset: early infancy
• Most common triggers  milk & soy
• Other foods: grains (rice, oats, barley), meat &
poultry, certain veggies & fruit (sweet potato,
squash, string beans, banana), legumes (peas,
lentils), seafood.
• Rice-induced FPIES  more likely to have severe
symptoms
• Reactions to breast milk reported (less likely)
Clinical features of FPIES
•
•
•
•
Vomiting (~2hrs post ingestion)
Diarrhea (~5hrs post ingestion)
Lethargy
Dehydration that may progress to:
– Acidemia
– Hypotension
– Methemoglobinemia
Labs and Biopsy Findings in FPIES
Laboratory Findings
• Possible elevated PMNs, eosinophilia, and
thrombocytosis occurring w/in several hrs after
ingestion
Biopsy Findings
• Colonic biopsies
– crypt abscesses, diffuse inflammatory cell infiltrate with
prominent plasma cells
• Small bowel biopsies
– acute inflammation, edema, and mild villous injury
• Focal erosive gastritis & esophagitis w/eosinophilia
also described
Allergy evaluation
• NON-IgE mediated
– Negative IgE testing (skin or blood test)
– Possible role for patch testing
(experimental)
Treatment of acute reaction
• Intravenous fluid boluses
• Supportive care
• Epinephrine, antihistamines,
and oral steroids
traditionally do NOT help
Definitions to know
• Food protein colitis
• FPIES
– Common
– Rare
– Milk, Soy
– Often breastfed infants
– Healthy infants who present
with blood or mucus in stool
– Symptoms subside after
removal of causative protein
– Resolves by 12mo
– Milk, Soy, grains, etc…
– Rare if exclusively breastfed
– Severe & protracted
vomiting, dehydration,
lethargy and shock few hrs
after ingestion
– Symptoms subside after
removal of causative protein
– Resolves by 1-3yrs of age
Management of FPIES
• Avoid suspected food
• Can usually continue breastfeeding (maternal
avoidance of offending food)
• Formula-fed & reacted to milk/soy:
– Sub hydrolyzed or preferably amino acid formula
• Caution with hydrolyzed formulas – consider medical
supervision w/first ingestion
– Do NOT sub cow’s milk formula for soy (or vice
versa) … 50% infants may react to both.
FPIES: prognosis
• Usually able to tolerate offending food
by 1-3yrs of age
• Recommend challenge under medical
supervision if food re-introduced
– IV access in patients w/history severe
reactions
Resources
• Food Allergy & Anaphylaxis Network
– www.foodallergy.org
• American Academy of Allergy, Asthma, and Immunology
– www.aaaai.org
• American College of Allergy, Asthma, and Immunology
– www.acaai.org
• APFED (American Partnership for Eosinophilic Disorders
– www.apfed.org
• The FPIES Foundation
– www.fpiesfoundation.org
• Center for Food Safety and Applied Nutrition
– www.cfsan.fda.gov
• US Food and Drug Administration Medwatch
– www.fda.gov/medwatch
The End
dnaimi@nwasthma.com
References
• Sicherer, SH, Teuber, S. Current approach to the diagnosis and
management of adverse reactions to foods. J Allergy Clin Immunol
2004; 114:1146
• Sampson, HA, Ho, DG. Relationship between food-specific IgE
concentrations and the risk of positive food challenges in children and
adolescents. J Allergy Clin Immunol 1997; 100:444.
• Sampson, HA. Utility of food-specific IgE concentrations in predicting
symptomatic food allergy. J Allergy Clin Immunol 2001; 107:891.
• Food allergy: a practice parameter. Ann Allergy Asthma Immunol
2006; 96:S1.
• Greer, FR, Sicherer, SH, Burks, AW. Effects of early nutritional
interventions on the development of atopic disease in infants and
children: the role of maternal dietary restriction, breastfeeding, timing
of introduction of complementary foods, and hydrolyzed formulas.
Pediatrics 2008; 121:183.
References
• Sampson HA, Munoz-Furlong A, Campbell RL. Et al. The second
symposium on the definition and management of anaphylaxis:
Summary report. J Allergy Clin Immunol 2006;117:391-7.
• Lieberman P, Kemp SF, Oppenheimer JJ, et al, The diagnosis and
management of anaphylaxis: An updated practice parameter. J Allergy
Clin Immunol 2005; 115 (3):S485-523.
• Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to
anaphylactic reactions to foods. J Allergy Clin Immunol 2001;
107(1):191-3.
• Sampson HA, Mendelson LM, Rosen JP. Fatal and near-fatal
anaphylactic reactions to food in children and adolescents. N Engl J
Med 1992; 327:380-4.
References
• Cianferoni A and Spergel JM. Food allergy: Review Classification
and Diagnosis. Allergology International 2009; 58: 457-466.
• Sampson HA and JA Anderson. Summary and Recommendations:
Classification of GI Manifestations due to Immunologic Reactions to
Foods in Infants and Young Children. J Pediatr GI Nutr 2000; 30:
S87-S94.
• Mehr S et al. Food Protein Induced Enterocolitis Syndrome--16 year
Experience. Pediatrics 2009;123:e467-472.
• Liacouras CA, et al. Eosinophilic esophagitis: updated consensus
recommendations for children and adults. J Allergy Clin Immunol.
2011 Jul;128(1):3-20.
• Sampson HA. Update on Food Allergies. JACI 2004;113: 805-819.
Additional References
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•
•
•
•
•
Sampson HA. Update on Food Allergies. JACI 2004;113: 805-819.
Cianferoni A and Spergel JM. Food allergy: Review Classification and
Diagnosis. Allergology International 2009; 58: 457-466.
Sampson HA and JA Anderson. Summary and Recommendations:
Classification of GI Manifestations due to Immunologic Reactions to Foods in
Infants and Young Children. J Pediatr GI Nutr 2000; 30: S87-S94.
Nowak-Wegrzyn, et al. Food Protein Induced Enterocolitis Syndrome--caused
by Solid Food Proteins. Pediatrics 2003;111:829-835.
Sicherer SH. Food protein induced enterocolitis syndrome: case presentations
and management lessons. JACI 2005;115:149-156.
Mehr S et al. Food Protein Induced Enterocolitis Syndrome--16 year
Experience. Pediatrics 2009;123:e467-472.