2:15 – 3 pm
Food Allergies and Food
Intolerance: Update on
Guidelines
SPEAKER
Maria Garcia-Lloret, MD
Presenter Disclosure Information
► Maria Garcia-Lloret, MD: No financial relationships to disclose.
The following relationships exist related to this presentation:
Off-Label/Investigational Discussion
► In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.
The
challenge
of
food
allergies
Maria I Garcia Lloret, MD
Division of Pediatric Allergy, Immunology and Rheumatology
Department of Pediatrics David Geffen School of Medicine
What
counts
as
a
food
allergy?
How
prevalent
are
food
allergies?
OK,
food
allergies
are
increasing.
But
why?
FOOD ALLERGY
IgE Mediated Non‐IgE Mediated
Eosinophilic Esophagitis Allergic Proctocolitis Food Protein Induced Enterocolitis
Not
All
Food
Allergies
are
Created
Equal
The
prevalence
of
food
allergy
in
children
is
somewhere
between
2
‐
8%
The
prevalence
of
peanut
allergy
quadrupled
from
1997
to
2010
2006
‐
2007
1.4 million
medical
encounters
for
food
allergy/anaphylaxis
Estimated
direct
costs
225 million
indirect
costs
115 million
The
economic
burden
of
food
allergic
reactions
in
the
US
Patel et al JACI July 2011
GENETIC PREDISPOSITION TO ATOPY COMPOSITION OF THE GUT MICROFLORA NON-ORAL EXPOSURE AMOUNT AND TIMING OF INTRODUCTION OF THE FOOD CROSS-REACTIVE ANTIGENS MEDICATIONS (ANTIBIOTICS, ANTIACIDS) PROCESSING OF THE FOOD EXPOSURE IN UTERO AND DURING LACTATION FOOD ALLERGY
WHY???
Functional
composition
of
the
gut
microbiome
strongly
affects
the
health
of
the
host
• Early colonization is critical for directing neonatal intestinal and immune development
• Germ free mice have reduced number of IgA producing plasma cells skewed T cell populations, and impaired tolerance to food allergens
• Commensal bacteria are involved in the breakdown and absorption of nutrients, the production of vitamins and hormones and the prevention of colonization by pathogens
• Differences in gut microbiota influence the absorption, bioavailability and metabolism of drugs
• Etc., etc., etc.
Multiple studies have shown that farm living is associated with less incidence of atopic disease
Infants from farming mothers display a distinctive signature of innate and adaptive immune activation 0 5 10 15 20 25 30 35 40 45 Asthma Atopy Farm Control
The
Hygiene
Hypothesis
Revisited
Challenging
the
“recommendations
”
•
2000
Milk 12 moEgg 24 mo Peanut 36 mo
•
2008
No evidence supporting the 2000recommendations: “limbo”
•
2015
Proofthat early introduction of peanutdecreases the incidence of peanut allergy
Learning
About
Peanut
Allergy
(LEAP)
Study
• Randomized, open label controlled study conducted in a single site in the UK
• 640 babies ages 4‐11 months at high risk for peanut allergy ( severe eczema, egg allergy or both )
• All infants were skin tested for peanut and most underwent an oral food challenge (OFC) with peanut
• Babies with large (> 4mm) positive skin test to peanut or babies that reacted to peanut consumption at the baseline OFC were excluded
• Two cohorts: 1) negative skin test ( not sensitized ) 2) positive skin test (sensitized)
• About half of infants in each cohort were randomized to either consume 6 grams of peanut protein per week or avoid all peanut
• Children were followed for a period of 60 months at the end of which they all underwent an OFC with 5 grams of peanut ( single dose )
• What happened?
86%
reduction
in
the
prevalence
of
peanut
allergy
in
the
active
group
Children avoiding peanut had larger skin tests and higher IgE against peanut than those eating this food regularlyEarly, sustained consumption of peanut products is associated with a substantial and significant decrease in the development of peanut allergy in
high‐risk infants
Trying
aspects
of
food
allergy
diagnosis
Financial
and
social
challenges
faced
by
food
allergic
patients
Present
and
future
therapeutic
options
Food
Allergy
:
Diagnosis
70%
20%
10%
Clinical historyLaboratory tests Food challenge
Food
allergies:
Clinical
presentation
•
>80%
patients
have
skin
manifestations:
flushing,
urticaria,
angioedema
•
Respiratory
symptoms
such
as
nasal
congestion
and
rhinorrhea
not
unusual
•
Gastrointestinal
complaints
also
frequent,
but
may
be
delayed
•
Signs
and
symptoms
•
Timing
of
the
reaction
in
relation
to
ingestion
•
Type
of
food
•
Prior
exposure
Food
allergy:
Testing
is
useful
•
Who
should
be
tested?
All
individuals
with
a
suspected
food
hypersensitivity.
•
When?
At
the
time
of
the
initial
presentation
•
Why?
To
institute
appropriate
dietary
and
pharmacological
management
“Skin
test”
Inexpensive Easy to perform Immediate results Detects tissue bound IgE
Not usually performed in
pediatric office Somewhat subjective Affected by medications
“Blood
test”
Widely available to primary physicians Allows to follow trend in repeated
determinations For some foods, levels indicate the risk
of a systemic reaction
Expensive False positives due to
crossreactive epitopes
False positive in patients with
very elevated total IgE
Both
types
of
tests
detect
sensitization
and
NOT
necessarily
clinical
reactivity
The
Oral
Food
Challenge
(OFC)
• Gold standard for the diagnosis of food allergies
• Should be performed by experienced medical personnel in a controlled environment
• Should follow standardized protocols
• High degree of patient satisfaction and improvement in quality of life
Food group Avoidingadmission on resultOFC positive OFCresult negative % Negative
Egg 23 5 18 78% Fruits 11 0 11 100% Milk 14 3 11 79% Peanut 10 3 7 70% Shellfish 1 0 1 100% Soy 13 3 10 77% Tree nuts 6 0 6 100% Wheat 5 1 4 80% Totals 122 20 102 84%
More
than
2/3
of
patients
with
presumed
clinical
food
allergy
who
undergo
an
oral
food
challenge
do
not
react
to
the
food.
Promising
new
diagnostic
modalities
Component Resolved Diagnostics (CRD)
Basophil Activation Test (BAT)
•
Flow
cytometry
‐
based
test
where
the
reaction
of
basophils
to
peanut
allergens
is
assessed
in
a
test
tube
•
Measures
the
levels
of
IgE
against
discrete
peanut
protein
allergens,
some
of
which
are
highly
associated
with
clinical
reactivity
Standard
of
Care
for
Food
Allergic
Patients
The recommendation
•
AVOIDANCE
•
Anaphylaxis
action
plan
•
Epinephrine
auto
injector
The challenge
Food
labelling
Hidden
sources
Accidental
exposures
Recognition
Access
to
medical
care
When
and
how
Cost
A
few
words
on
the
auto
‐
injectors
•
Underprescribed
•
Underutilized
•
Inadequate
dosing
•
Inadequate
format
Standard
of
Care
for
Food
Allergic
Patients:
Special
considerations
•
General
belief
that
certain
vaccines
are
contraindicated
in
egg
allergic
patients
but
this
is
not
supported
by
large
epidemiological
studies
•
Per
current
CDC
guidelines
MMR
is
safe
for
all
patients
with
a
history
of
egg
allergy
•
Influenza
vaccines
also
considered
safe
in
egg
allergic
patients.
•
CDC
current
recommendations
make
an
exception
for
those
patients
that
react
to
egg
in
all
forms
and
have
a
history
of
anaphylaxis
to
this
food
Options
for
patients
with
severe
egg
allergy
‐
Flublock (
RIV3,
recombinant,
egg
free)
in
patients
older
than
18
years
old.
‐
For
younger
patients
or
if
Flublock not
available
administer
IIV
in
clinic
if
comfortable
recognizing
and
managing
systemic
allergic
reactions.
Monitor
for
30
min
‐
Flumist not
recommended
AND
SPEAKING
OF
ANAPHYLAXIS
•
DEFINITION
Serious
allergic
reaction
that
is
rapid
in
onset
and
may
cause
death.
“I
KNOW
IT
WHEN
I
SEE
IT”
CLINICAL CRITERIA FOR ANAPHYLAXIS
Acute onset (minutes to hours)
Skin and/or mucosal tissue + 1
• Respiratory compromise
• Reduced BP,collapse, syncope
Exposure to alikely allergen +2
• Skin/mucosal signs
• Respiratory compromise
• Reduced BP,collapse
• Persistent GI symptoms
Exposure to aknown allergen
• Low systolic BP
Management
of
Anaphylaxis
•
Patient
recumbent
with
elevated
extremities
•
Epinephrine
x1
or
more
q
5
‐
15
minutes
•
Beta
Agonists
•
Fluid
Resuscitation
• Antihistamines (H1 and H2)
• Glucocorticoids
• Methylene Blue
A
few
other
aspects
to
bear
in
mind
•
High
parental
and
patient
anxiety
•
Limited
family
activities
•
Social
isolation
•
Bullying
What
is
allergen
immunotherapy
(AIT)?
•
Administration
of
gradually
increasing
doses
of
allergen
that
modify
the
immune
response
in
a
way
that
decreases
clinical
reactivity
.
•
It
is
the
only
available
treatment
capable
of
modifying
the
course
of
allergic
disease.
AIT
Tolerance
Desensitization
• Transient increase in the threshold of clinical reactivity. • Effect lost upon
discontinuation
• Permanent change in the immune response resulting in long lasting protection irrespective of ongoing exposure
AIT
Routes
of
Administration
•
Subcutaneous
•
Oral (OIT)
•
Sublingual (SLIT)
•
Epicutaneous (EPIT)
•
Intralymphatic
Rush desensitization Build‐up MaintenanceEfficacy
is
assessed
by
OFC
while
on
treatment
(desensitization)
and
while
off
therapy
(tolerance
)
Days
Weeks to months
Months to years
•
50+
clinical
trials
assessing
the
efficacy
of
OIT
for
food
allergy
•
Reported
outcomes
promising
for
egg
and
peanut,
showing
“favorable
response”
in
about
50%
of
patients
•
Many
children
with
an
initial
favorable
response
regained
their
clinical
reactivity
a
few
months
after
discontinuing
therapy
•
Too
soon
to
tell
if
this
form
of
OIT
can
promote
tolerance
VIPES study: Easing the concern about
accidental exposures and more
• DBPC
• 221 peanut allergic patients
• Patch with 50,100 or 250 mcg of peanut protein
• Daily application over 12 mo
0 10 20 30 40 50 60 Placebo Peanut 250 % R esponde
rs Children ( 6‐11) in the active arm
were on average able to consume 1000 mg of peanut protein or at least 10 fold more than at baseline
Favorable immunological changes: Decrease in IgE, increase in IgG4
TAKE
HOME
POINTS
•
Early
introduction
of
peanut
(
and
possibly
other
common
food
allergens)
reduces
the
risk
of
peanut
allergy
later
in
life.
•
High
risk
infants
(
eczema,
other
food
allergies
)
MUST
be
evaluated/tested
by
an
allergist
prior
to
the
introduction
of
highly
allergenic
foods
•
Food
challenges
are
the
gold
standard
at
the
time
of
diagnosing
a
true
food
allergy
and
should
be
recommended
more
often
TAKE
HOME
POINTS
•
OIT
is
feasible
but
at
present
not
recommended
outside
the
clinical
research
setting
•
EPIT
promising
“bridge”
therapy
that
increases
the
threshold
of
clinical
reactivity
•
New
diagnostic
modalities
may
better
discriminate
between
sensitized
and
clinically
reactive
patients
Case
1
•
8
month
old
infant
•
Extensive
atopic
dermatitis
with
frequent
flares
•
Exclusively
breastfed
for
six
months
•
Eating
pureed
fruits
and
vegetables
with
no
problems,
but
developed
hives
after
eating
a
small
amount
of
egg
white
•
What next??
What
we
know
•
50%
babies
with
eczema
show
evidence
of
egg
sensitization
•
Many
will
react
to
raw
or
lightly
cooked
egg
but
will
tolerate
highly
denatured
egg
•
Babies
with
eczema
and
egg
sensitization
are
at
a
high
risk
of
peanut
allergy
What
we
can
do
•
Confirm
the
diagnosis
of
egg
allergy
(blood
test
or
skin
test
)
•
Consider
challenge
with
baked
egg
•
Assess
for
the
presence
of
peanut
sensitization
•
If
peanut
tests
are
negative,
introduce
peanut
in
the
diet
•
If
peanut
tests
are
positive,
consider
oral
challenge
with
peanut
The
Next
• Kindergartener
• Extensive eczema, resolved • Diagnosed with peanut allergy by a
blood test at age 2 (peanut IgE 5 KU) • Avoiding peanuts and tree nuts ever
since
• Family is very worried because there are no “allergen free” schools in her district and they are thinking of moving to another area or home schooling
•
What
next?
Case
2
What we know
•
A
positive
test
does
not
always
imply
clinical
reactivity
•
Up
to
20%
of
children
with
peanut
allergy
outgrow
their
condition
•
Only
a
third
of
children
with
peanut
allergy
are
also
allergic
to
tree
nuts
What we can do
• Reassess the level of peanut specific IgE
• If value is 20 kU or above, likely peanut allergic
• Consider oral challenge and inclusion in protocol of oral immunotherapy • If value is 5 kU and below, do
challenge with peanut • Value between 5 and 20 “ grey
zone”
• Consider risk factors, consider peanut challenge • Reassess tree nut sensitization
•
29
year
old
junior
executive
•
Exercise
induced
asthma
•
Known
lactose
intolerance
•
1
year
history
of
bloating,
abdominal
pain
and
fatigue
with
multiple
other
foods
•
Symptoms
have
become
more
severe
in
the
last
two
months
•
A
friend
told
her
the
problem
could
be
gluten
•
What
next?
Case
3
What we know
• Food intoleranceusually due to incomplete
or poor digestion due to an absolute or
relative enzymatic deficiency. “Dose
dependent”. Symptoms restricted to the GI
tract
• Available tests can confirm lactose
intolerance
• Food sensitivity presumably due to an as yet
undefined immune reaction. Patients report
a variety of symptoms in addition to GI
• Overlap between IBS and food sensitivity
• Non‐celiac gluten sensitivity is a disorder
gaining some acceptance in the medical
community
• There are NO VALID tests for food
sensitivities
What we can do
• Thorough physical exam and history,
including dietary history.
• Consider labs : nutritional assessment
(Vitamin D), IgE for wheat and celiac
screening .
• If the above are negative, consider dietary
exclusion for 6 weeks
• DO NOT request food specific IGG or
IGG4 panel
( expensive, not validated )
• If symptoms dramatically improve, you
may have your answer. If not, look for
other etiologies.
