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Food Allergy
Adverse Food Reactions
Non-immunologic
Toxic / Pharmacologic
Bacterial food
poisoning
Heavy metal poisoning
Scombroid fish
poisoning
Caffeine
Alcohol
Histamine
Adapted from Sicherer S, Sampson H. J Allergy Clin Immunol
2006;117:S470-475.
Non-Toxic / Intolerance
Lactase deficiency
Galactosemia
Pancreatic insufficiency
Gallbladder / liver
disease
Hiatal hernia
Gustatory rhinitis
Anorexia nervosa
Idiosyncratic
Adverse Food Reactions
Immunologic
IgE-Mediated
(most common)
Systemic
(Anaphylaxis)
Oral Allergy
Syndrome
Immediate
gastrointestinal
allergy
Asthma/rhinitis
Urticaria
Morbilliform rashes
and flushing
Contact urticaria
Non-IgE Mediated
Cell-Mediated
Eosinophilic
esophagitis
Protein-Induced
Enterocolitis
Eosinophilic gastritis
Protein-Induced
Enteropathy
Eosinophilic
gastroenteritis
Atopic dermatitis
Eosinophilic proctitis
Dermatitis herpetiformis
Contact dermatitis
Sampson H. J Allergy Clin Immunol 2004;113:805-9, Chapman J et al. Ann Allergy Asthma
& Immunol 2006;96:S51-68.
Public Perception
25% of the population – at least 1 member of
their family had “food allergy”
Adults surveyed – 20% report they have a
“food intolerance” and alter their diet for
perceived adverse reaction to food
Prevalence – Food Allergy in Children
What is the est. prevalence under 3 yrs old?

6% (2004)
Fish – 0.1%
Shellfish – 0.1%
Tree nuts – 0.2%
Soy – 0.4%
Wheat – 0.4%
Food Additives – 0.5-1%
Peanut – 0.8% (0.5-1%)
Egg – 1.3% (2003) young kids
Cow’s milk allergy – in 1st yr – 2.5%
Asthmatic kids – 6% food induced wheezing
Mod to severe AD – 35% food allergies
Prevalence - Food Allergy in Adults
What is est. prevalence in adults?
 3-4% U.S. (3.7% - 2004), (2% - 1999)
Food additives – 0.01-0.23%
Fish – 0.4%
Tree nut – 0.5%
Peanut – 0.6% (Total peanut & tree nut 1.1%)
Shellfish – (2% - 2004), (0.5% - 1996)
Fruits, veggies – common (~5%) but not severe
Sesame – increasingly reported
Adults with AD – rare food allergy
Adults with asthma – rare food allergy
Natural History
Milk allergy – 50% lose reactivity by 1 yrs,
70% by 2 yrs, 85% by 3 yrs

35% with milk IgE at 1 year had other food
allergies by 3 yrs, 25% had FA at 10 yrs
Egg, soy & wheat – 80% resolve by school age
Peanut allergy – What percent lose reactivity?

20% by age 5 (1998, 2003), but it may recur
Adults can also lose reactivity with avoidance
Skin test can remain + but no rxn on DBPCFC
CASE: Crustacean Allergy: IgE Towards
Protein in the Food, NOT Iodine
79 year old man had anaphylaxis to shrimp at age 20, 25
Doctors told him he was allergic to iodine in seafood
Avoided seafood, iodized salt for years
Age 70: retirement dinner, hostess picked shrimp out of his portio
and gave it to him --- ER visit for anaphylaxis
At age 79, specific IgE measurement extremely high to shrimp:
>100 kU/L
On follow-up after education on avoidance, happily consuming
foods with iodized salt because he didn’t have to screen salt
source any more
Gastrointestinal Barriers to Ingested
Food Antigens
Immunologic barriers
Block penetration of ingested antigens:
Antigen-specific s-IgA in gut lumen
Clear antigens penetrating GI barrier:
Serum antigen-specific IgA and IgG
Reticulo-endothelial system
Physiologic barriers
Breakdown of ingested antigens:
Gastric acid and pepsins
Pancreatic enzymes
Intestinal enzymes
Intestinal epithelial cell lysozyme
activity
Block penetration of ingested antigens:
Intestinal mucus coat (glycocalyx)
Intestinal microvillus membrane
composition
Intestinal peristalsis
Figure 2-15 The mucosal immune system
GALT – induces tolerance
M Cells overlie Peyer’s Patches (PPs),
primarily in distal small intestine
M cells have lectin-like receptors which
sample antigens (large) from gut lumen
Ags taken-up by macrophages and carried
to resident T and B cells in PPs
All Ig classes can be produced after oral
antigen, IgM+ B cells primarily switched to
IgA+ B cells
Oral Tolerance
Figure 10-1 Fates of
lymphocytes after
encounter with
antigens
Deletion – only with very high antigen dose
Anergy
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Intestinal epithelial cells (IECs) – non-professional
APC’s – Class II MHC, but no 2nd signals
Dendritic cells in PPs (non-inflam environment) express
IL10 and IL4 which favor tolerance
Failure of Oral
Tolerance
Figure 19-1 Sequence of events in
immediate hypersensitivity reactions
Food-specific IgE Abs bind
to FcER1 on mast cells and
basos
Exposure to Ag - immediate
release of vasoactive
amines (histamine) – hives,
wheezing, shock
Delayed or chronic
response - cell mediated or
cytokine release (TNF-a, IL5) and most commonly
affect gut
Oral Allergy Syndrome/PollenFood Allergy Syndrome
Mucosal equivalent of urticaria
Itching and swelling of the mouth & oropharynx
May lead to refusal of the food
Assoc with rhino-conjunctivitis and pollen allergy
Birch – apple, cherry, pear, kiwi, carrot, potato,
celery, hazelnut
Mugwort – Carrot, celery, parsley, fennel
Ragweed – Melon, banana
Grass – Kiwi, watermelon, tomato, potato
Sx may improve with allergy immunotherapy
Can treat with anti-histamines
Latex-Fruit
Syndrome
30-50% of those with latex allergy are sensitive
to some fruits due to cross-reactive IgE
Most common fruits: banana, avocado, kiwi,
chestnut but other fruits and nuts have been
reported
Can clinically present as anaphylaxis to fruit
Warn latex-sensitive patients of potential crossreactivity
Some fruit-allergic patients may be at risk for
latex allergy
Evaluation of Food Allergies
History:
1.
2.
3.
4.
5.
What food responsible?
Quantity of food
Time course
Similar prior symptoms
Other factors necessary (exercise,
fevers, EtoH)
6. When was last reaction?
Food diaries – causal foods, “hidden”
ingredients
Skin Testing
Skin Prick test – 95% negative predictive value in
people > 3 yrs – If negative SPT – food challenge
In kids < 3 years, only 80-85% negative predictive
value
Only 50% PPV – IgE present, but they can tolerate
the food (atopic derm)
Wheal 3 mm greater than neg. Wheal 8 mm.
If positive prick with convincing history of
anaphylaxis – restrict the food
Fatalities reported after intradermal testing
Fruits, veggies (apples, orange, bananas, potatoes,
carrots, celery) – extract not stable – prick-prick
Testing
Older RASTs and paper disk 1st gen EIAs
Quantitative specific IgE (CAP-FEIA;
Pharmacia) – 2nd generation – predictive
values for reactions
Suspect non-IgE – biopsy of gut, skin
Suspect non-allergic – sweat, breath H+,
endoscopy
Unproven/experimental –
provocation/neutralization, cytotoxic tests,
kinesiology, hair analysis, IgG4
Levels of Specific IgE Yielding
Predictive Values for CAP-RAST Tests
Food
Milk
95 % positive
predictive value
32
95 % negative
predictive value
0.8
Egg
6
90 % at 0.6
Peanut
15
85 % at <0.35
50% at 65
2
75 % at > 100
5
20
0.9
Soy
Wheat
Fish
Sampson HA, Ho DG. J Allergy Clin Immunol 1997;100:444-51.
Elimination Diets and Food
Challenges
Elimination Diets
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Eliminate suspected food(s), or
Prescribe limited “eat only” diet, or
Elemental diet
Oral Challenge (MD, Crash cart)
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Open
Single-blind
Gold Standard to diagnose FAs – DBPCFC
If DBPCFC is negative, must follow w open
challenge (1-3% false neg challenge)
Anaphylaxis
94% of fatal food anaphylaxis involve
peanuts or tree nuts (63% peanut, 31%
tree)*
Fatalities Due To Anaphylaxis To
Foods*
32 fatal cases from 1994-1999 analyzed
Peanut accounted for 63% of fatalities
 Other nuts: 31%
All ingestions were “accidental”
84% occurred outside of home
All but 1 had asthma (97%)
Epinephrine was NOT given or was given very
late in 88%
*JACI 2001;107:191-193
Treatment: Education
Anaphylactic Symptoms
Erythema, flushing or pruritus
Urticaria and angioedema
Nasal, ocular, and palatal pruritus
Sense of impending doom
Gastrointestinal symptoms
Uterine cramps
Dizziness, syncope, loss of
consciousness
Anaphylactic Symptoms
Upper airway obstruction
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Hoarseness
Dysphonia (altered voice)
Difficulty swallowing.
Lower airway obstruction
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Wheezing
Chest tightness
Treatment: Avoidance…
Easier Said Than Done
www.foodallergy.org - FAAN
25% of labels may not reflect presence of peanut1
Sensitive patients may react to trace amounts of
peanut (as low as 100 mcg)
Contact with or inhalation of peanut might occur
on airlines2
Cross Contamination (shared equipment)
Hidden ingredients
Most common places:
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Asian restaurants, bakeries and ice cream shops.
Desserts
1.www.cfsan.fda.gov/~dms/alrgpart.html
2. JACI 1999;104:186-9
Epinephrine
Children: 0.01 ml/kg,
maximum of 0.5 ml

Repeated every 5-15 minutes
for two doses and then every 4
hours (more if needed)
Adult: 0.3 ml to 0.5 ml of a
1:1000 dilution
subcutaneously or
intramuscularly

Repeated every 5 to 15 minutes
(more PRN)
Less than 20 kg – Epi Pen Jr
(0.15 mg)
Over 30 kg – Epi Pen (0.3 mg)
Between 20-30 kg – Depends
on history

If asthma, h/o anaphylaxis, or
peanut allergy – Give higher
(adult) dose 0.3 mg
Fatal and near-fatal anaphylactic reactions to food
in children and adolescents*
6 fatal
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Symptoms 3-30 minutes
Only 2 had epinephrine in first hour
3 Uniphasic, rapid progression
3 Biphasic: Early mild symptoms followed by 12 hours asymptomatic; then resp and CV sx
7 non-fatal
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Symptoms within 5 minutes
7/7 received epinephrine within 30 minutes
4 Uniphasic: Severe symptoms w/in 30 minutes
3 Protracted anaphylaxis: Ventilatory support
and vasopressor meds for > 24 hours (one for 3
weeks!)
www.americanmedical-id.com
Food Allergy
Action Plan
Other Medications…
H1 receptor antagonist (Diphenhydramine Benadryl)

1 to 2 mg/kg or 25 to 50 mg/dose parenterally
Ranitidine (Zantac)
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H2 receptor antagonist
When combined with an H1 type may be useful in
reversing hypotension refractory to
epinephrine and intravascular fluid replacement
Adult Dose: 50 mg/dose IV/IM q6-8h
Albuterol, racemic Epinephrine
Other Medications
Glucagon

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1-5 mg (20-30 mcg/kg) over 5 min by infusion of 515 mcg/min titrated to clinical response
Maintains blood pressure independent of
adrenergic receptors by increasing intracellular
cyclic AMP
Stimulates release of endogenous catecholamines
Corticosteroids
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200 mg hydrocortisone IV
Efficacy of corticosteroids in acute anaphylaxis or
in reducing a late anaphylactic reaction has not
been clearly established
Can Food Allergies be
Prevented? 50 year debate
Who should we target?
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“Allergy Genes” – Genome Project – 11q13
(IgE receptor), 5q31-33 (cytokine genes), 6p21
(HLA-D region)
Family history – 1 allergic parent – risk atopy
40-60%, 2 allergic parents – 60-80%
Sensitivity of fam hx in predicting food allergy
only 45%, specificity is 74%
Cord blood IgE – 26% sensitive, 74% specific
Both fam hx plus cord blood IgE – Sensitivity
56%
Maternal Avoidance
IgE sensitization to food during gestation
is RARE - < 0.3%
Maternal avoidance of milk and egg during
pregnancy not better than infant avoidance
– not recommended
Risk of maternal malnutrition
No harm in recommending peanut
avoidance
Primary Prevention
Breastfeeding – Inconclusive Evidence
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Even if Moms avoid allergenic foods – the
results can be transient
Food allergens can pass into breast milk
Breastmilk can have immunostimulatory or
immunosuppressive effects on the infant’s
intestine
Cytokine content differs in allergenic and nonallergenic mothers
Exclusive breastfeeding can decrease infant
serum IgE, decrease atopic derm and asthma
Exclusive breastfeeding during 1st 4-6 mos &
continuation until 1 year is recommended
Lactation Avoidance Diets
Conflicting studies
Most show it is protective to avoid allergenic
foods – less atopic derm and food allergies
Consider avoiding peanuts and tree nuts
Most likely don’t need to avoid egg, cow’s milk
and fish
Ensure 1500 mg/day of elemental calcium
Delay solids?
High risk of allergy, delay solids to 6 mos old

Finnish study 1983 – 6 mos BF – 14% rate
eczema; Food < 6 mos – 35% eczema
Delay cow’s milk or dairy to > 1 year
Avoid cow’s milk and soy formulas if possible

Use hydrolyzed hypoallergenic formula
Delay eggs until 2 years
Delay peanuts, nuts, and fish until 3 years
Anti IgE – Xolair (Omalizumab)
Food challenge with encapsulated peanut
flour – determined threshold
4 SQ injections at 4 week intervals
2-4 weeks after had repeat challenge
Increase tolerance from
½ peanut to 9 peanuts
Dose dependent
tolerance*
25% of group showed
no improvement
*NEJM 2003;348:986-93
Other Therapies
Traditional Chinese herbs – efficacy in
murine-model of peanut induced
anaphylaxis – starting human trials
Engineered proteins that lack IgE binding
sites, engineered chimeric molecules with
allergen and Fc-gamma, coadministration
of TH-1 promoting adjuvants (CpG and
heat-killed bacteria)
Summary
Patient history is very important
Determine IgE vs. non-IgE mediated
Diagnosis by judicious testing, elimination and
challenge
Avoidance/education/preparation for emergencies
are current therapies
No conclusive studies indicating that manipulation of
the mother’s diet during pregnancy or lactation or
the restriction of allergenic foods from the infant’s
diet will prevent the development of food allergy
Periodic re-challenge to monitor tolerance as
indicated by history, allergen and level of food
specific IgE
References
Sampson HA. Middleton Ch 89 – Adverse
Reactions to Foods
Sicherer SH, Sampson HA. Mini-primer.
Ch 9. Food Allergy.J Allergy Clin Immunol
2006; 117:s470-475.
Sampson HA. Primer. Ch 9. Food
Allergy.J Allergy Clin Immunol 2003;
111:s540-547.
MKSAP – Allergy and Clinical
Immunology. Ch 4 – Food Allergy. Pages
194-208