food allergy prevention, detection and...
TRANSCRIPT
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Food Allergy Prevention, Detection and Treatment
Scott H. Sicherer, MD
Jaffe Professor of Pediatrics, Allergy and Immunology
NJAAP Annual Conference
May 11, 2016
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I have no relevant financial or commercial interests to disclose.
I do not intend to discuss an unapproved or investigative use of a commercial product or device in my presentation.
After the presentation you should
-Understand new concepts in allergy prevention
-Understand limitations and utility of allergy tests
-Advise families on emergency management
Disclosures and Learning
Objectives
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Tests Available
• History
• Prick skin test
• Serum IgE (allergen specific)
– Extracted whole proteins
– Components
• Oral Food Challenge
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Serum Specific
IgE, “RAST”
• Blood test that measures specific IgE
• Not affected by antihistamines
• Slightly less sensitive than prick skin tests
• More costly than skin tests, wait for results
• Negative - virtually eliminates IgE-mediated allergy
• Positive - not proof of symptomatic allergy
• Reported in various ways: “Classes” “Counts” and “kU/L”
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Evaluation of
Suspected Food Allergy
• To differentiate “allergy” (~3-5% affected by an immune response) from other adverse reactions (~20% avoid food for perceived adverse reactions)– e.g., non-allergic adverse reactions include: intolerance (lactase
deficiency), toxic effects (food poisoning), pharmacologic effects (caffeine)
• To confirm a food as a cause of a typical allergic reaction when food is a suspected trigger – e.g., urticaria, angioedema, wheezing, anaphylaxis, etc.,
proximate to ingestion
• To evaluate the role of foods in chronic disease– e.g., moderate-severe atopic dermatitis in children, allergic
gastrointestinal disorders
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Predictive Values Vary By Study (patient
selection, criteria of allergic, age, illness,
food, history)Food >50% React >95% react >95% (< age 1-2)
Milk IgE 2 kU/L IgE 15 kU/L IgE 5 kU/L
Egg IgE 2 kU/L IgE 7 kU/L IgE 2 kU/L
Peanut IgE 2 kU/L (history)
IgE 5 kU/L (no history)
IgE 14 kU/L
Fish IgE 20 kU/L
Walnut IgE 18 kU/L
Reviewed in: Järvinen KM, Sicherer SH. Diagnostic oral food challenges: Procedures and biomarkers. J
Immunol Methods. 2012; 383(1-2):30-8. also Peters JACI 2013;132;874.
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Cross Reactivity
8
Sicherer
JACI
2003;108(6):881-90
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9
Component Testing: Peanut
Ara h 1
Ara h 2
Ara h 3
Ara h 6
CCD Ara h 9Ara h 8
Not all parts are
equal!
-
These are “stable”
proteins associated
with true allergy.
Ara h 2 is best
associated with
reactions
Still, “level” counts
These are pollen-
related, unstable
proteins
Stable but
uncommon in the
US
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IgE Test Limitations• Few studies available that correlate clinical reaction to
test results– Results vary by food, age, and, to some extent, research center
• Reactions could occur despite a “negative” test– Several studies show reaction rates over 20% in patients with
“undetectable” food specific serum IgE (with suspected allergy by history)
– Allergist may perform prick skin test with commercial extract and/or fresh food for increased sensitivity. May undertake supervised oral food challenge to confirm allergy or tolerance
• Cross-reactivity
• Results do not predict severity
• THEREFORE: – 1) Avoid indiscriminate “panels” of screening tests
– 2) Apply “prior probability” (reasoning from the history) for test selection/interpretation
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History
1) 4 year old ingested peanut and developed hives. IgE to peanut 4.5 kU/L. Ara h 2 1.5 kU/L. Diagnosis?
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History
1) 4 year old ingested peanut and developed hives. IgE to peanut 4.5 kU/L. Ara h 2 1.5 kU/L.
2) Had eaten peanut routinely up to the day of reaction
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History
1) 4 year old ingested peanut and developed hives. IgE to peanut 4.5 kU/L. Ara h 2 1.5 kU/L.
2) Had eaten peanut routinely up to the day of reaction.
3) Hives lasted 3 days
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Diagnosis
• Based on history, tests
• Suggest consultation with a Board-Certified Allergist-Immunologist
• Guidance in:
– Clinical Report: Sicherer SH, Wood RA; the SECTION ON ALLERGY AND IMMUNOLOGY. Allergy Testing in Childhood: Using Allergen-Specific IgE Tests. Pediatrics. 2012; 129(1):193-197.
– Expert Panel:Boyce J. et al . NIAID-Sponsored Expert Panel Report: Guidelines for the diagnosis and treatment of food allergy in the United States. J Allergy Clin Immunol 2010 (Dec), S1-58.
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Management:
Dietary Avoidance
• Hidden ingredients (peanut in sauces or egg
rolls)
• Labeling issues (“spices”, changes, errors)
– Labeling laws cover plain English for milk, egg,
wheat, soy, peanut, tree nuts, fish, Crustacean
shellfish
– Advisory labeling is voluntary (“may contain”)
• Cross contamination (shared equipment)
• “Code words” (“Natural flavor”)
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CDC’s Voluntary Guidelines
• Result of 2011 FDA Food Safety
Modernization Act
• To support implementation of food allergy
management and prevention
• Includes instructions for multiple
stakeholders: Parental obligations (relates
to physician diagnosis and plans),
individualized plans, communication
strategies, risk reduction, education of
stakeholders, response to anaphylaxis, etc.
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Autoinjector Dosing• Manufacturer says 0.15 mg for 33-66 lbs and 0.3 mg
for 66 lbs and over
• For infants, ampules/syringe may be too awkward
• Conclusion: Switch from 0.15 mg to 0.3 mg at about 55 lbs (25 kg)
Weight Options (fixed dose
injectors)
Implication
Under 10 kg 0.15 mg dose At least 1.5 fold
overdose
15 kg 0.15 mg dose Perfect
20 kg 0.15 mg dose
0.3 mg dose
1.3 fold under-dose
1.5 fold overdose
25 kg 0.15 mg dose
0.3 mg dose
1.7 fold under-dose
1.2 fold over-dose
>=30 kg 0.3 mg dose Perfect, with increasing
underdose
Clinical Report: Sicherer SH, Simons FE. Self-injectable epinephrine for first-aid management of anaphylaxis.
Pediatrics. 2007;119(3):638-46.
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Resource:
www.foodallergy.org/actionplan.pdf
Written Plan and Medical Jewelry
Consider cetirizine
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Summary About
Epinephrine• Should be available promptly, but within reason (e.g.,
not in every classroom)– Not locked up
• If allowable, child might carry but discuss risk/benefit
• Instructions must address health professional versus delegates
• Antihistamines are comfort care, does not stop anaphylaxis
• Bronchodilators should not be depended upon to treat anaphylaxis
• Argument for having an unassigned dose available (25% of school anaphylaxis without a prior diagnosis*)
*McIntyre CL et al Pediatrics 2005;116:1134-40
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Sicherer et al JACI 2010; 125:1322-6
Peanut Allergy
Appears to Have Increased
Peanut Allergy
(Children < 18 yrs)
by Year of
Telephone Survey
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1997 2002 2008
Peanut Allergy
Peanut AllergyPer
cent
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There are theories about the increase in
food allergies
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What are “normal” feeding practices?
▶ Breast feed
▶ Weaning
▶ Solids that are easily managed by an infant
▶ Progression as teeth erupt
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Dietary Prevention
Program, US
▶ Randomized, prospective, 288 subjects, one parent with allergy
▶ Program:– Pregnancy, 3rd trimester-no milk, egg, peanut,
reduced soy/wheat
– Lactation, avoid same, supplement casein hydrolysate
– Solids at 6 mo, 12 mo-dairy, wheat, soy, 24 mo-egg, 36 mo-peanut, fish
▶ Followed to age 7 years
Zeiger JACI 1989;Zeiger PAI 1992;Zeiger JACI 1995
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Dietary Prevention Program, US
Period Prevalence of Disorders
Zeiger JACI 1989;Zeiger
PAI 1992;Zeiger JACI 1995
0
5
10
15
20
25
30
35
%
Age 1 Age 2 Age 4 Age 7
Asthma
0
5
10
15
20
25
30
35
%
Age 1 Age 2 Age 4 Age 7
Atopic dermatitis
0
5
10
15
20
25
30
35
%
Age 1 Age 2 Age 4 Age 7
Food Allergy
Prophylaxis
No diet
*
*
In 2000, American Academy of Pediatrics
suggested this feeding approach
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Egg Introduction and Egg Allergy
Koplin et al JACI 2010
RR (95% CI)
0 0.1 0.5 1 2 5 10
4-6 mo
7-9 mo
>12 mo
10-12 mo
“HealthNuts” study, 2589 infants population-based, cross-sectional study
Effects seen in high-risk and low-risk infants with cooked egg
introduction
Adjusted for confounding factors
Confirmed egg allergy
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Risk Factors for Peanut Allergy
Lack et al N Engl J Med 2003
YES RISK NO RISK
TopicalExposure to
Creams Containing
Peanut
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Peanut Allergy Prevalence
Du Toit JACI 2008
0.17% 1.85%
Infant Peanut Consumption
7.1 Grams/mo 0 Grams/mo
The American Academy of Pediatrics
rescinded prior avoidance advice….
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Exposure Theory
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Eczema severity augments impact of
household peanut exposure
Brough, Liu, Sicherer J Allergy Clin Immunol 2015;135:164-70
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Source: Sicherer SH and Sampson HA. “Peanut allergy: Emerging concepts and approaches for an apparent epidemic.” J Allergy Clin Immunol 120(3): 491-503.
Peanut
Allergy
Genetic predispositionto peanut allergy
Genetic
predispositionAtopic
Dermatitis
Dietary &Environmental
Exposures
Use ofAntacids
Ingestion of cross-reactiveproteins (soy)
Topicalexposure
Pollenproteins
Manner of processing
Frequency
of ingestion
Timing
Dose
Maternal ingestion
during pregnancy
Maternal ingestion
during breast feeding
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Du Toit G et al. N Engl J Med 2015;372:803-813
LEAP (Learning Early About Peanut) Study
High risk infants (eczema/egg allergy), 4-11 months age
Negative or small peanut skin tests
Randomized to eat (vs. avoid) peanut to age 5 years
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Interim Guidelines
• Infant 4-6 month with allergic problems such as severe eczema, egg allergy
• Evaluate for food allergy (to peanut) with skin test
• Introduce peanut like in LEAP study and maintain in diet (presumed under medical observation)
• Emphasize unknowns (dose, permanency)
• Emphasize 2008 American Academy of Pediatric Report: No reason to avoid allergens in healthy infant
Fleischer, Sicherer, Greenhawt et al. J Allergy Clin Immunol 2015;136:258-61
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The EAT Study: UK, unselected,
randomized to eat allergens early (3 mo)
Perkin MR et al. N Engl J Med 2016;374:1733-1743.
Evaluated milk, egg,
wheat, soy, peanut,
sesame, fish. 3
month versus 6
month.
Intention to treat: no
difference.
Per protocol,
reduced egg, peanut.
Only one-third met
per protocol.
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What are “normal” feeding practices?
▶ Breast feed
▶ Weaning
▶ Solids that are easily managed by an infant
▶ Progression as teeth erupt
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What are “normal” feeding practices?
▶ Breast feed
▶ Weaning
▶ Solids that are easily managed by an infant via pre-mastication
▶ Progression as teeth erupt
18% of surveyed Brooklyn mothers (HIV+)
premasticated food (Hafeez Arch Pediatr Adolesc Med 2011;165:92-93)
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Atopy at 18 months in relation to
pacifier use and cleaning practices
Hesselmar B et al. Pediatrics 2013;131:e1829-e1837
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“Clueless” actress Alicia Silverstone
“He literally crawls across the room to attack my mouth if I’m eating”
Fox News asked medical and nutritional experts what they thought of the feeding
method for humans.
'It doesn't seem like a hygienic practice,' one doctor told the site.
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Key References
▶ Sicherer SH, Wood RA. Clinical Report: Allergy testing in childhood: Using
allergen-specific IgE tests. Pediatrics. 2012 Jan;129(1):193-7.
▶ Sicherer SH, Mahr T; the Section on Allergy and Immunology. Clinical Report:
Management of Food Allergy in the School Setting. Pediatrics. 2010
Dec;126(6):1232-1239.
▶ Sicherer SH, Simons FE. Clinical Report: Self-injectable epinephrine for first-aid
management of anaphylaxis. Pediatrics. Pediatrics. 2007 Mar;119(3):638-46.
▶ Boyce J. et al . NIAID-Sponsored Expert Panel Report: Guidelines for the
diagnosis and treatment of food allergy in the United States. J Allergy Clin
Immunol 2010 (Dec), S1-58.
▶ Sampson HA, Aceves S, Bock SA, James J, Jones S, Lang D, Nadeau K,
Nowak-Wegrzyn A, Oppenheimer J, Perry TT, Randolph C, Sicherer SH, Simon
RA, Vickery BP, Wood R. Food allergy: A practice parameter update-2014. J
Allergy Clin Immunol. 2014; 134(5):1016-25.
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Thank you