Diagnostic Techniques
For
Food Allergy Treatment
George F. Kroker, MD FACAAI
Types of Food Reactions
 Toxic Reactions
 Food Intolerance
 IgE mediated
 Non IgE mediated (type III or IV)
 Combined IgE and cell mediated
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IgE Mediated Food Allergy—
Diagnostic Tools
 Skin Prick Testing (SPT)
 In Vitro Testing
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Skin Prick Testing for Foods
 More sensitive, less specific
 SPT100% sensitive in anaphylactic
range
 PPV only 40-50% in usual cases
 Predictive value : wheal 8mm > neg ctrl
 More reliable in children than adults
 More reliable if done with fresh foods
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In Vitro Testing for IgE Food
Allergy
 Safer, less invasive than SPT
 Reliable, especially in younger children
 False negatives, 10% or less
 (Niggermann B)
 Total/specific IgE very high in AD, so
clinical correlation advised
 Specific IgE cutoff values established
with 95% PPV anaphylaxis
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In Vitro Test: Typical Pt
Screen
“Maximum yield—minimal cost”
 Total IgE
 “Common Food” panel: eggs, milk, wheat, corn,
yeast + “any food they eat a lot” and any food
with a history of prior clinical reactivity, especially
foods suspected of causing anaphylaxis
 If sensitive to specific pollens or latex, consider
testing for concomitant food allergens
 Measure specific IgE to strongest clinically
relevant inhalant allergen(s) by history/skin test
as another “benchmark”
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In Vitro Test Interpretation:
Clinical Considerations
 Two allergens may have similarly positive scores,


but differ markedly in the clinical symptoms elicited
(i.e. have different “target organs”)
A food allergen may have a falsely low IgE score if it
has been avoided for a prolonged period
Remember: you are measuring systemic unbound
IgE—studies show that sometimes one may not
detect systemic elevation in IgE yet when local
mucosa is analyzed (nasally & in the gut) one may
detect elevated allergen-specific IgE
 The “x-ray” analogy
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In Vitro Test Interpretation:
Clinical Considerations (Cont)
 “After additional analysis, if the ELISA test
results (or skin testing) remain inconsistent
with the patient’s clinical history, the
overriding criteria in making the final
diagnosis should be the clinical history and
physical examination…”
Pearls and pitfalls of allergy diagnostic testing: report from the
ACAAI/AAAAI Specific IgE Test Task Force. Cox, L et al. Annals of Allergy,
Asthma and Immunology. Dec 2008;101:580-592
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ELISA Food Test—a limitation
 “Measuring the whole food may not tell
the whole story”
 Certain components of a food may be
more allergenic than others—how can
we investigate this? Is it clinically
relevant?
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Oral Allergy Syndrome (OAS)
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Pollen-Food Allergy Syndrome
 Oral pruritus and edema, laryngeal
edema, reported anaphylaxis
 Ragweed pollen: melons, bananas
 Birch pollen: apple, hazelnut, peaches,
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Allergen Component Diagnostic
Testing
 New type of allergy testing available
through Thermo Fisher
 www.pirllab.com
 Addresses limitations of current ELISA:
 Current
tests define allergen sources, not
specific allergenic molecules
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Allergen Component
Diagnostic Testing
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Panallergens of Importance
 PR-10 proteins (BetV1 homologue)
 Heat
labile, causes OAS
 Lipid Transfer Proteins (LTP)
 Heat
stable, systemic reactions
 Profilins
 Seldom
cause serious clinical symptoms
 Tropomyosins
 Cross-reactivity
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shellfish, mites, cockroach
Conformational vs Linear Epitopes
E G G
E G
G
E
E
G
G
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G
G
Component Resolved Diagnosis in Food Allergy. Sadudee
Boonmee, MD.
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Component Resolved Diagnosis in Food Allergy. Sadudee
Boonmee MD
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Component Resolved Diagnosis in Food Allergy. Sadudee
Boonmee MD
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Component Resolved Diagnosis in Food Allergy. Sadudee
Boonmee MD
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Clinical Utility of Component
Testing
 Reveals original sensitizing source
 Risk estimation for severity of reactions
 Risk estimation for reaction to cooked
food
 Resolving cross-reactivity issues
 Establishing priorities for
immunotherapy
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Food Component Testing:
Clinical Utility: Example #1
 “Is my child at high risk of peanut
anaphylaxis with a very positive
peanut ELISA test?”
 Solution—do peanut component test:
 Elevated r Ara h 2 ?—yes!
 Elevated r Ara h 8—no!
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Food Component Testing:
Clinical Utility: Example #2
 “My child is ELISA positive to egg—
what does this mean?”
 Ovomucoid -: tolerance to hardboiled egg and egg in baked goods
 Ovomucoid +: confirmed egg allergy;
will not tolerate any kind of egg
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Component Testing and LCM:
Conclusions
 Component testing may be of help in in
establishing priorities in SLIT treatment
 Assessment
may direct treatment priority in
a patient with multiple fruit sensitivities
 Example: a patient with birch pollen allergy
and OAS symptoms from apple, peach,
cherries could benefit from aggressive
treatment of birch allergen if Bet v 1
positive on testing
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The Mystery of Delayed Food
Reactions
The most beautiful thing we can experience is the mysterious.
It is the source of all true Art and Science
--Albert Einstein
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Immediate vs. delayed food
reactions
IgE mediated
Non-IgE, delayed onset
Patient population
Pediatric predominant
Adult predominant
Symptom onset
Minutes, hours
18-36 hours
Types of symptoms
Urticaria, wheezing,
congestion etc.
Fatigue, myalgia, CNS,
IBS, Headache, etc.
Often identified by pt
Yes
No
Standard Lab test
Yes (IgE)
No
Well documented in
medical literature
Yes
No
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Delayed-Onset Food
Sensitivity Clues
 Pts often present with a diagnosis of
chronic fatigue syndrome, irritable bowel
syndrome, fibromyalgia, migraine
 Patient may have “cravings” for certain
foods, and eat them excessively
 Unexpected dietary changes may result in
unexpected changes in baseline symptoms
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Delayed-Onset Food Sensitivity
Case Examples (Cont.)
 Patient tries a high protein diet for weight
loss and feels “wonderful”
 Patient travels overseas and headaches
go away
 Patient visits sister and in 3 days her
fibromyalgia “disappears”
 Colonoscopy prep makes symptoms
disappear
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Delayed-Onset Food Sensitivity
“Clinical Pearls”
 May play a role in IBS, CFS,
fibromyalgia
 Delayed food allergy often co-exists
with delayed inhalant allergy
 Patients often sick “the day after…”
 Cravings for a food often present;
sugar cravings suggest Candida
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Delayed-Onset Food Sensitivity
“Clinical Pearls”
 Multiple delayed food allergies often
signal heightened intestinal
permeability (i.e, “leaky gut”)
 Rapid weight gain and loss suggests
fluctuating edema from delayed
onset food allergies
 Gluten and Candida can cross-react
due to “molecular mimicry”
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Delayed-Onset Food Sensitivity:
The Problems
 “A bad illness in search of a good test”
 Usually standard IgE tests are
negative; no widely accepted test avail
 Paucity of scientific studies on tests to
reliably determine diagnosis
 Lack of interest by allergy profession
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Delayed-Onset Food Sensitivity
Commercial Tests
 IgG ELISA

http://www.gdx.net/product/10145
 ALCAT

https://www.alcat.com/
 Mediator Release Test (MRT)

http://nowleap.com/mediator-release-testing/mrt-iii/
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Delayed Food Sensitivity
Testing
 There is no uniformly accepted in-vitro
test for Delayed Food Sensitivity
 The gold standard remains a rigorous
trial of an elimination diet, followed by
challenge
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IgG ELISA Test
 Food-specific IgG may be either
protective or pathologic
 Principle of testing is the same as
measuring IgE but using IgG instead
 Multiple labs provide test—Genova
Diagnostics, Meridian Valley, etc.
 May have more inter-lab reproducibility
than cell-based assays
Reproducibility and Reliability of Two Food Allergy Testing Methods. Hodsdon, et
al. Natural Medicine Journal, March 2010.
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IgG Food Antibody Studies
 Randomized controlled trial of food
elimination diet based on IgG antibodies for
the prevention of migraine like headaches

Mitchell N et al. Nutr J 3022 Aug 11;10:85
 Variable food-specific IgG antibody levels in
healthy and symptomatic Chinese Adults

Zeng et. Al Plos one 8(1) e53612 (epub) 2013
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IgG Food Antibody Studies
 Diet restriction in migraine, based on IgG
against foods: a clinical double-blind
randomized cross-over trial

Alpay K et al. Cephalgia (7):829-37. 2010
 The value of eliminating foods according to
food-specific immunoglobulin G antibodies in
irritable bowel syndrome with diarrhea

Guo H et al. J Int Med Res 40(1):204-210, 2012
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ALCAT Test
The ALCAT test: An Evaluation of Efficacy and Clinical Applicability.
Andrea Martinson
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Mediator Release Test
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Delayed Food Allergy Tests:
Problems
 Specificity, sensitivity, reproducibility
not universally validated
 False positives occur frequently,
especially at levels of low reactivity
 False negatives occur:
 Food
previously avoided
 Food reaction non-immunologic
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Delayed-Onset Food Sensitivity
Implementation of Test Results
 Commercial tests serve as only an
initial screening tool for clinical
interpretation and diet design
 “Gold standard” for diagnosing is an
elimination/challenge diet
 Never put pt on open-ended long term
diet based on these blood tests
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Diagnostic Testing Summary
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One Final Thought…
 “In the diagnosis of food allergy and food sensitivity,
the best tool available to the practicing allergist is not
the test results he holds in his hands, but the grey
matter between his ears”
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Thank you
Next:
Treating Food Allergy
Mary Morris MD
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