Can We Finally Eat That Peanut? | Corinne Keet, M.D., Ph.D.


Our next speaker
is Corinne Keet. Corinne is an expert in
allergies in children, particularly food allergies. And she’ll be
talking to us about, can we finally eat that peanut? Thank you.>>Thank you, so-
>>[INAUDIBLE]>>Thank you, so I’m a pediatric allergist and
epidemiologist and a clinical researcher. So my perspective is a little
bit less in the lab and more on the population level. And I wanted to talk about our
really big changes we’ve had in our ways of preventing peanut
allergies really this last year or so too. But first to talk about
food allergy overall, so food allergy is a specific
immune response like we’ve been talking about day. All these immune responses
a specific immune response to a food most commonly occurs
because of IgE antibodies, a specific kind of antibody.>>That occur, that are formed
by exposure to the food and require this prior exposure
to have a reaction. There is currently no FDA
approved treatment for food allergy, although there
are two medications or two pharmaceutical products
that are in phase 3 trials. That I don’t have time
to talk about today but I would be happy to
talk about anytime. So right now,
the only excepted management of food allergy is to
avoid the food and use epinephrine if needed for
reactions, epipen. In general, food allergy
appears to be increasing and pretty rapidly. In particular, peanut allergy is the one the
seems to be increasing rapidly. Food allergy goes along
with other diseases, and particularly is closely tied to
excema or atopic dermatitis, depending on the allergists and
dermatologists. They call it different things,
which is a major risk factor for food allergies. So, what I want to talk about
today is about very big changes we’ve had in the prevention
of peanut allergy which are reflected in the guidelines
from our national organizations. Which in 2000,
suggested that it would be, although they were
not very conclusive. They suggested that it would be
reasonable to delay peanut until age three, as well as
other allergenic foods and promoted breast
feeding at that time. By 2008, our National Society
said, well, actually, there’s really not
very much data, so we’re retracting
that recommendation. You should do what you want. We have no data. And then this year, in January,
the new guidelines say that actually, if you are at high
risk of peanut allergy because you have eczema, or
have another food allergy. Really infants should be eating
peanut-containing foods as early as four to six months. So I want to talk a little
bit about how we got to the guidelines in 2000 and how what’s happened
changed since then. And I think that the story
is instructive about some of the payrolls of
making guidelines and about how we deal with evidence. So if you actually look at
the 2000 guidelines, they’re really not focused on peanut
allergy on introducing solid. So if you look at
the title at the bottom, the title of the talk,
these guidelines were drawing from this actually about
hypoallergenic infant formulas. And really there was focus was
on whether infant with high risk of food allergy should
breast feed longer and should introduce more
hypoallergenic formulas. And then as a beside,
they said well since we’re giving these recommendations,
it seems reasonable, even though we don’t have much
data to say we should delay allergenic foods to tell
a year for milk, two years for egg and three years for
peanut, fish and shellfish. But as we’ll see,
there was very little data. And these were really response
to very significant changes that have been made in the 20th
century about infant feeding. But if you look back, there’s
no real garden of Eden for infant feeding. Long as we’ve had human
civilization, people have tried to find alternatives to breast
feeding either by necessity, or because they wanted to. So as early as 4,000 years ago,
there were infant feeder, usually this would be cows or goats milk that infants
would be feed at that time. By the 19 century, these
were more sophisticated, but these methods were because of
the lack of hygiene that was available and the lack of
nutritional knowledge. Most of the infants
were not breast fed or artificially fed and
actually ended up dying. And the most common way for
people who were not able to breast feed to was to employ
another woman to breast feed for their child. In certain classes, this was very wide-spread
in certain times. So, it wasn’t really
until the 20th century, the early 20th century, that
formulas became to be patented. We had clea water, and
the ability to wash bottles so that the infant wouldn’t
die when you fed them breast milk from humans. And so by the 1940’s, actually
most infants were going home from the hospital on
infant formula and not on breastfeeding. And along with this came changes
in the way other foods were introduced and with the
commercialization of baby foods whereas previously maybe
infants were fed gruel. I think it was quite a variety
of ways that people were fed or the parents chewed the food for
them Which introduces a lot of bacteria,
which may have an effect. This commercialization
of baby foods led, was promoted more, earlier and
earlier introduction. And this, I don’t know if
you can see, in the 1960s, was a infant guide which
suggested that solid food should be introduced at two
to three days of age. That strained meats by 14 days,
by 5 weeks eggs, and that at 9 weeks the infant just like dad
should be eating bacon and eggs. [LAUGH]
>>[LAUGH]>>And you can see throughout all of this that infant
feeding is really tied up in our views about how an infant
should relate to the mother, what mothers are doing besides
feeding their child and how independent
infants should be. So in the 1960s compared to
earlier in the century, most infants were being fed, starting
to be fed foods other than milk at four to six weeks compared
to four to seven months earlier. And accompanying
all these changes, there was a pretty big backlash. It started in the 1930s. People started to say that they
thought eczema was related to some of this infant
formula feeding. That there was this increase in
eczema, and the infant formula, at that time, did have some
nutritional deficits that probably were even more
associated with eczema, beyond the issues
of breastfeeding. And then over the following
decades, there was more evidence, although pretty weak,
about that breastfeeding was protective against eczema and
these allergic diseases. And then by the 1980s,
the formula companies started to develop new formulas
that were hydrolyzed, where the milk proteins
were broken down. And those started to be tested
in randomized studies about Prevention of food allergy. There were some studies that
combined this with delay in solids, but there were
actually no studies that looks specifically at whether delaying
prevented peanut allergy. But overall, these as well as
some of the basic science led to this theory that in infancy, similarly to what
the previous speaker, that there was a particularly
leaky gut in early infancy. And that the immune system was
really proallergenic at that time, and if we delayed
the introduction of allergens, we might be able to
prevent allergy. And that’s what led to
those 2000 recommendations. But over the next decade that
people started to say well, is this really the best thing. So even though people started
to delay allergens longer and longer, there was still more and
more food allergy. And so the story is one of
the authors of this paper Gideon Lack, who is a professor
in the UK is giving a talk about peanut allergy. And one of the people in
the audience was an Israeli pathologist, and he said,
we really don’t have much peanut allergy in Israel,
and I wonder why. And so they did
an epidemiological study and found that the rate of peanut
allergy among Jewish children in the UK was about ten times that
of Jewish children in Israel. 0.17 percent in Israel compared
to almost 2 percent in the UK. And they also noted, this is
not kind of study that they can establish causality, but they
also noted that Israeli infants typically ate a teething
food that was peanut. It’s called Bamba which is
like a peanut Cheeto and it, because of
the Kosher Dietary Laws, that’s a common snack
that is eaten in Israel. And so infants in Israel were
eating about seven grams of peanuts a month compared to
none for most British infants. So they suggested that this
might be the reason and that maybe we had
it all backwards. And then they did a clinical
trial that was done in the UK, but funded by the NIH. And the story goes it’s because
it was considered to risky in the US, although I’m not
100% how true that is. But they took infants who
are 4 to 11 months of age with severe eczema or egg allergy,
with the highest risk infants. They split them into two. One half they said, don’t eat any peanut products
until five years of age. And the other half, eat it
at least three times a week. And they did exclude about 11%
because they had a big enough skin prick test that they
thought they were already allergic. But they included those who have
smaller than they were thought were less likely to be allergic. And then I guess
you can’t see but the final outcome was
determined by food challenge. So that food challenge at
five years of age they said are you allergic or not? Let’s feed you peanut and see. That’s our gold standard
in food allergy for when we decide [LAUGH]
>>[LAUGH]>>if you’re allergic or not. And the people who were
in the avoidance group, 17% of those kids had peanut
allergy at five years of age, compared to only 3% in
the consumption group, and most of this 3% were peanut
allergic when they were infants. So this an 82% reduction, which
is really, really large for prevention studies, and
so this really changed, this was a randomized control
trial, our sort of highest level of evidence, and changed how
we thought about things, and this is what led to
the newest guidelines. So the newest guidelines came
together as an NH sponsored meeting of the various
pediatric and allergenic committees, and
they, after some discussion, said that infants who had
severe eczema or egg allergy. So this is really based
largely on that trial, that they should introduce
peanut as early as four to six months of age, this is
a little bit controversial. Other parts of the document say
that that should be introduced at four to six months of age,
or whether it should be later, we actually don’t have much data
about four to six months or a little bit later. And they also recommend for the first time in an allergy
setting that these infants should have testing before
they introduce peanut. Previous guidelines have all
said you should see whether you have allergy by
eating a food and not by testing
before you have it. For other infants with
more mild eczema, they should introduce maybe
around six months of age. And for everyone else, they
should introduce at an age and culturally appropriate way,
so, you might ask, what about other foods? There’s not just peanut allergy,
egg allergy is actually more common, there’s now been about
six studies done of egg allergy, some of them show benefits,
some of them don’t. But what they all show is that
when they use this egg powder, which four of the studies have
done, concentrated egg powder, that a large number
of infants react. Much more than you would expect,
based on what we know, generally, about egg allergy, so
it seems to be very allergenic. The studies of baked egg,
or egg when it’s baked, it’s broken down,
those seem to be better. We don’t have guidelines yet,
and they’re not in the process of making guidelines, but if I
were to make the guidelines, I would make them about using
more cooked or baked egg for prevention of egg allergy. We have no studies yet of tree
nuts, fish, or shellfish, and these allergies tend to have
a different natural history, and the milk data is
difficult to interpret. So, I think, just to reflect
on how we went wrong, I think we gave these broad
sweeping recommendations based on really very low
quality evidence. And although there were caveats
in the recommendations, I think it’s very hard for those to be translated into the
actual practice of pediatrics. We recommend things or
we don’t, we don’t say, well, we don’t know, maybe it is,
maybe it’s not, by the time it gets to people’s lives,
those caveats are ignored. We reason from faulty
mechanistic theories, we gave in to the pressure to do something,
and I think this one worries me, we underestimate the potential
harm from our guidelines. So I just wanted to close with
the questions that keep me up at night about this field,
that beyond what, I think, we all worry about it, as well
as beyond the funding issues. But I worry about the unintended
consequences of our new guidelines, which I worry about
whether this recommendation for screening will lead to more
false diagnoses of food allergy. Because food allergy testing
is very poor, and we know that there are a lot of people who
test positive who don`t really have the disease, and the only
way to know is to feed the food. I worry that our screening will
overwhelm our available medical resources, and I also worry
whether people will actually introduce peanut earlier,
the people that need to introduce it, or whether
there will be too much anxiety. And then I don’t have to time to
talk about the new treatments, but I am happy to talk
to anybody individually. I do worry about these
treatments as well, about the long term outcomes, about questions of what
exactly what we’re treating. I just wanted to put these out
here as issues that we could talk about some time, and whether these will lead to
more reactions, or fewer. And if there may be other ways
to reduce anxiety and improve freedom in children’s lives
that may be less medicalized. So I’m open to questions,
there’s a lot of things that are changing in this field, and
I think it’s very exciting.>>[APPLAUSE]>>Yes, I’m wondering if there is any other relationship with
developmental progress eczema associated with whether people
are immunized, so to speak, whether they are breastfeed,
and so forth, later in life.>>Yeah, so the sort of current
theory is that eczema causes food allergy because exposure
to the allergens through irritated skin leads to
an allergic response versus exposure to the mouth
that leads to tolerance. And so there are studies going
on about trying to improve the eczema by using
a moisturizer from birth and whether that might reduce
the risk of allergies, is that your question,
does that answer your question?>>I was wondering more about
whether there was a common mechanism associated with food
allergies and the eczema, and whether avoiding the
development of food allergies caused less
progression of eczema.>>Yeah, so, it’s been a major
controversy in the field about why eczema and food allergies
are so closely related. Is it because there’s a common
immune defect that causes them both, common genetics
that cause them both, or is that the eczema is
causing the food allergy, or is the food allergy
causing the eczema? And I think probably all of
those things are true for some patients, but
overall more and more evidence is accumulating
that eczema itself causes food allergies because of
the skin barrier break down. Some of that evidence is
genetics defects in the skin barrier, causing an increased
risk of food allergy. And some of it is mouse models
and other models that show if you irritate the skin,
inflame the skin, and you put food on it,
then you get an immune response, so there are attempts to prevent
that process through skincare. In terms of whether treating
food allergy makes eczema less, I am not aware of
studies of that, but it’s an interesting question.>>Hi, that was super
fascinating, thank you, my question is maybe a little
more like nitty gritty than your broad talk.>>Mh-hm, yeah.>>So when people develop
peanut allergies, is it known, is it an appropriate immune
response to a specific protein in the peanut or different
proteins in the peanut? And, if so, is there any
structural similarity to some protein on a worm or
a pathogen or something?>>Yeah, so,
that’s a great question. So, there are different peanut
proteins and some of the, you can be sensitized to
different peanut proteins. There’s one called ERH2, which is a seed storage protein
that tends to be the most people who have true peanut
allergy are sensitized to. There are peanut
allergy proteins, one called ERH8,
which these are just numbered, that has homology with
pollen allergies and people who are sensitized more to that
tend to have more mild symptoms. In terms of why certain proteins
are a cause for allergy and other proteins don’t, which I
think is maybe underlining your question, some of them,
we know that a few things that cause allergy tend to
be heat resistant. So they’re the things that
are broken down in the early processes of digestion,
don’t tend to cause systematic reactions or
cause major allergy. They, some of them have
endosomatic activity, so they sort of mimic danger,
I don’t think for the peanut we know why peanut, things like
dust mite, they do have, within the dust mite itself,
causes an immune response. There’s some people I know in
the audience have studied this more in the laboratory, but we do know that some allergens
have caused certain immune responses besides the antigen
specificity, yes?>>As a follow up
to that question, is there a possibility to
develop a genetically modified peanut that maybe takes out
some of those properties?>>Yeah, people are working
on that, there are people who are working on taking out the
major allergens in the peanut. Personally, I don’t really
understand that so much, because it’s not really gonna, I
think, to be able to take it out so that somebody who is
peanut allergic could eat it. It seems unlikely that you would
be able to completely remove the allergens, but perhaps you could use
those things as treatment. Because, if there was a little
bit of allergenicity and you’ve sort of built up
tolerance to it, but there are efforts underway,
in North Carolina, there’s a company that’s
trying to do that.>>I was just wondering what
the latest is on breastfeeding, does breastfeeding provide
protective effect for all food allergies, or
some, or different, or?>>So, the current official
guidelines are still that breastfeeding helps
prevent food allergies. I think when you
look at the studies, they’re more weak than perhaps
that evidence suggests, but there are so many other reasons
to breastfeed, besides allergy, that I think are very strong. In terms of, I don’t know
if this is your question, but there were, used to be
recommendations that mothers should avoid certain foods
during breastfeeding, and there really is very
little data for that. What there is data for
is if you try to avoid milk and egg during breastfeeding,
or pregnancy, that it leads to nutritional
complications for the mother. But there’s not good evidence
one way or another about whether eating foods while you’re
breastfeeding increases or decreases a food allergy.>>Can you talk just a little
bit about the treatments?>>Yeah.>>For these allergies,
medical and non-medical, is lotion the only non-medical?>>No, well, so, I guess it depends on how you
declassify things, in general, for allergy, for hundreds of
years, we’ve done immunotherapy, where you get allergy shots, put
in a little bit of an allergen, and you build up immune
tolerance to that. When they tried to do that
in the 80s for food allergy, people died, because
the immune response is so strong, but in the last 15 years
or so, people have started to do oral immunotherapy, where you
build up small amounts slowly. And there are people in practice
who are using that, and there are companies who are now
developing a more standardized method of that by oral
immunotherapy to build that up. There are also patches, so,
the same idea, generally, of an allergen, but
this is put through the skin. I know I just told you that
the skin may cause allergy, but apparently that’s not
entirely all the time true. If you have it through intact
skin, over time, that may reduce the amount that somebody
reacts to an allergen as well, does that answer your question,
or?>>Yeah, and the non-medical is?>>Well, so
you could do the medical, the oral immunotherapy
at home or in a practice by just eating
small amounts of the food, but the problem is it’s very small
amounts and the people have a lot of reactions
during these treatments. And so that’s why the main
allergy community says we really don’t think that it’s ready and is something that can be used in
medical practice right now, but that’s one of the approaches
that’s been used.>>Thank you very much.>>Sure.>>[APPLAUSE]

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