Examination of Witnesses (Questions 649-659)
PROFESSOR JOHN
HARPER, PROFESSOR
JONATHAN HOURIHANE,
DR WARREN
HYER AND
DR MARK
ROSENTHAL
7 MARCH 2007
Q649Chairman: I am Lady Finlay, I am chairing
this Sub-Committee and this is our tenth public hearing in our
inquiry into allergy. I would like to welcome you as witnesses
today and, also, members of the public who have come for this
session. There is a note declaring the interests of Members of
the Committee, so we will not be going through declaring our own
interests during the session. We would like to go through and
ask you questions, and it would be helpful, because we have a
lot of things we want to cover, if we can try to keep answers
fairly tight so that we can move on. I hope everyone will contribute
to the session. I wonder if I could start by asking you each just
to introduce yourself and then I will go into questioning.
Professor Harper: I am Professor John Harper
from Great Ormond Street Hospital and the Institute of Child Health
in London.
Professor Hourihane: I am Professor Jonathan
Hourihane, from the University College, Cork in Ireland.
Dr Rosenthal: Dr Mark Rosenthal from the Royal
Brompton Hospital in Chelsea.
Dr Hyer: I am Dr Warren Hyer, from Northwick
Park and St Mark's Hospital in northwest London.
Q650 Chairman: Thank you. I wonder
if you could start off by telling us how the prevalence and clinical
spectrum of allergic diseases differs between adults and children.
Professor Harper: I am a paediatric dermatologist,
so my take on this subject really relates mainly to atopic dermatitis,
or eczema, in association with allergy. Eczema is a major part
of my work. The prevalence in children ranges from 10 to 15 per
cent, and there have been some studies approaching 20 per cent.
So it is a very common problem. It is primarily a clinical issue
in childhood, particularly children under the age of five, but
the predisposition to developing atopic dermatitis, or eczema,
does not really go away. Something like 10 per cent of adults
still get eczema from time to time, and in a smaller percentage,
maybe around one per cent, this is quite severe. So eczema is
right across the whole age range, and is primarily a problem of
children. I do not know whether you want me to develop further,
but the prevalence seems to be increasing which has been documented
in a number of studies. It is a worldwide problem with some countries
having a much higher incidence of eczema than others.
Professor Hourihane: I am a paediatric allergist,
so my particular interest is in food allergy. There is data to
show the prevalence of peanut allergy in the United Kingdom has
trebled since 1996 from 0.6 per cent to 1.8 per cent, which is
one in 55 children. Other food allergies are less common in older
children but the burden of allergic disease with food allergy
is borne by the pre-school child, and it may be that up to 6 or
8 per cent of pre-school children will have experienced an allergic
reaction to food by the time they go to school. There is attrition
of this prevalence to about 2 per cent in adults with food allergy,
and I think the other witnesses will talk about asthma. The issue
about food allergy being a minor problem which then evolves into
asthma appears, maybe, not to be correct any more because the
allergies that children are having now are the ones that are known
to persist into adulthood. So we may see a hardcore of up to 3
per cent, I imagine, with serious allergies, like peanut and shellfish,
etc.
Dr Rosenthal: I am a respiratory paediatrician
and, therefore, my slant is on asthma as well as food allergy.
Certainly asthma has increased quite a lot over the last 50 or
60 years, but is probably plateauing-off as a recent study has
suggested, or possibly even falling. I agree that the concept
that asthma is allergic is far too simplistic as asthma covers
a very wide spectrum of conditions whose final common pathway
of symptoms are very similar. Therefore, it would be a mistake
to say that asthma was an allergic condition only.
Dr Hyer: Specifically to answer your question
about why it is different to adults, I see this as a paediatrician
who serves the population as well as a paediatric gastroenterologist.
The difference with my children compared to adults is children
often suffer many different manifestations of atopy. So if they
have peanut allergy they may have very severe eczema. If they
have peanut allergy their asthma is a greater risk for a life-threatening
event. There are much more multi-organ issues in childhood than
there are in adults, where it may be that only one manifestation
of atopy will persist. As a consequence, the workload that has
come forward to a simple district general hospital has been suffocating
in its volume of children with complex, multiple allergies, who
may just start with eczema, and it may be very severe eczema,
and persist with potentially very serious restrictive multiple
food allergies as they get older. I think this is a big difference
and has been well-documented in good quality, prospective studies
looking at the natural history of these children with very complex
multiple food allergies.
Q651 Chairman: Thank you very much.
I wonder if you could also explain something else to us. The conditions
such as asthma, rhinitis and eczema can have allergic and can
have non-allergic etiological backgrounds. I wondered whether
the balance of allergy, and true allergy, that it plays in these
conditions is different in the childhood population to the adult,
whether allergy is more difficult to diagnose in the childhood
population and whether the balance of importance of allergy on
life is greater or lesser in children than in adults. I do not
know if you are able to answer that.
Professor Harper: In relation to eczema, I think
that we need to recognise that a proportion of children with eczema
also are susceptible to allergy. You can certainly have children
with eczema who do not have allergy as a major problem but a proportion
do, and this can be very difficult. The data as to what percentage
that is is variable depending upon which age groups are looked
at and how they define eczema. It is complex because we do not
understand the relationship between eczema and allergy very well.
In those that do suffer with allergy as an issue, allergic reactions
can be a major factor in making the eczema worse. So you need
to address that almost as a separate issue. This is a situation
that is mainly seen in children, and as they go into adult life
several of these common allergies, like cows' milk, become better
tolerated and only a few allergens persist as a significant problem
in adult life, such as peanuts and, maybe, kiwi fruit.
Dr Hyer: In relation to food allergy, food allergy,
as you have already heard, is principally an issue for pre-school
children. So its relationship to eczema, for example, will mean
that allergens and food allergens are more likely to be associated
with that. We know that children with severe eczema, for example,
carry a 50 to 60 per cent chance of having significant food allergy.
That data is not supported in adult practice. So if you take,
for example, eczema, from my perspective, you can see that food
allergy has a significant role in a significant proportion of
children. That has been validated by international data and that
is not concurrent with what happens in adult practice, so there
must be a skew to greater allergic phenomena in children.
Professor Hourihane: Part of your question was:
is it more difficult to diagnose allergies in children. It is
if you have got nobody to make the diagnosis.
Dr Rosenthal: I would say, from an asthma perspective,
that allergy in the sense we are discussing it, is the cause of
a relatively small proportion of asthma in childhood. There are
a lot more important environmental or other precipitants of asthma
than allergy.
Q652 Lord Haskel: Professor Harper
said that some countries have a higher prevalence of eczema than
others. Is there any pattern to this? Is it less developed countries
or more developed countries?
Professor Harper: There is data. I do not know
how reproducible this data is but there are studies that show
a lower incidence in developing countries compared to more Westernised
countries. Also, migrant populations; those coming from developing
countries to the UK or the USA are more likely to develop eczema.
It is really complicated. It is not quite clear what these environmental
factors are but it does seem that Westernisation is relevant in
some way.
Dr Hyer: We know that the prevalence of allergic
diseases differs even within developed countries, and certain
parts of Australia and certain parts of Europe carry a much higher
prevalence, of which the UK (certainly from within the ISAAC study)
does not favour well; we have some of the highest prevalence of
allergic disorders than anywhere else in Europe. Professor Hourihane
may be able to validate that.
Professor Hourihane: What I would like to say
is that in less Westernised parts of the world, such as Western
Africa, they can eat peanuts at the age of six or eight months
without ever developing peanut allergy. So maybe it is related
to the environment, the nature of the food allergen and its timing
of introduction. Peanut is not the problem all the way around
the world that we have the perception it might be in the UK.
Q653 Lord Taverne: A recent article
by the International Study of Asthma and Allergies in Childhood
found there was a rise in the prevalence of allergy symptoms,
particularly in the 6-7 year-old age group. I find the picture
rather confusing: I heard Professor Harper say that across the
whole age range there is a prevalence of eczema increasing; from
someone else that asthma was, perhaps, falling; there is more
multi-organ allergies in children, and Dr Mark Rosenthal's statement
that we have here suggests that there has been a modest true increase
but it may be stabilising. Do you see an increase at the moment,
particularly amongst children? If so, what is the reason for it
and what can be done about it?
Professor Hourihane: You may have heard from
other witnesses in previous sittings about the hygiene hypothesis,
which appears to be the most plausible or most robust of the explanations.
I think there is not much more to say. That is what we think is
the reason. It appears that allergic conditions are the price
that a small proportion of our population pay for the way the
entire population lives.
Dr Hyer: Just so it is not focused on the 6-7
year-old, which is the outcome from the ISAAC study, there are
numerous studies (and there are at least seven studies in the
UK) which looked at the prevalence of allergy and which validate
that it happens across many age ranges, and not just limited to
the 6-7 which was reported in that specific study. That data can
be looked at throughout the UK, it can be looked at throughout
Germany and many other parts of Europe. So I think it is important
not just to assume that there is a rise in one specific age group.
Q654 Lord Taverne: Are there signs
of a plateau? Stabilisation?
Dr Hyer: There will be a bias for how data is
validated and the quality of the data collected because, of course,
allergy is quite trendy and people may over-report. From a clinical
perspective, I have had to change my practice in a district general
hospital because I can no longer practise paediatric gastroenterology
without tackling allergy. This was not the same issue 14 or 15
years ago when I started my training. The prevalence of peanut
allergy is such that it has now reached, as we heard, around about
1 in 55. The allergy to agents such as tree-nuts and to fruits
and pollens did not exist in my practice 20 years ago. I have
kept my eyes open during that time, and I do not know whether
it has plateau-ed but I have certainly seen it rise.
Professor Harper: We can make these clinical
observations and you can ask why, but there are many unanswered
questions. We really do not know the answer. It is interesting
that Professor Hourihane mentioned the "hygiene hypothesis",
and that actually is all it is, a hypothesis; that is, cleanliness
and the lack of exposure to viruses and bacteria may make you
more susceptible. However, the opposite is not true; if you actually
have children who are exposed to infection there is no evidence
whatsoever that this reduces your risk of allergy or atopic dermatitis.
In fact, there are many papers on infection in early life triggering
eczema and asthma. So it is a hypothesis.
Dr Rosenthal: I might slightly demur on that
one in that there have been good studies from Germany, Switzerland
and Austria showing the effect of being pregnant and attending
to farm animals and whether the child after birth also got into
the barn, and their risks of having asthma at the age of seven
was reduced almost to zero compared to other farmers whose wives,
when pregnant, did not go into the barn or have contact with animals.
So exposure in early life certainly affects something, though
why does remain completely unanswered. So you can see from the
various answers that this is a highly complex problem of which
we only know a very tiny amount.
Dr Hyer: There will be more than just the hygiene
hypothesis to account for this. People have looked at diet, polyunsaturated
fats, cereals, grains, the way food is prepared, breastfeeding
practices, nutrition during breastfeeding. All of these—in
fact, Gross National Product of your country can also predict
your risk of atopy. There are such complexities that the hygiene
hypothesis alone is a very valid hypothesis but it is made so
much more complicated than that.
Q655 Lord Taverne: It has already
been mentioned, but I was going to ask, whether early viral or
bacterial infections predisposed infants to the development of
allergies.
Dr Rosenthal: If you take studies of American
day-care inmates, so to speak, they will have far more viral illnesses
and virus-associated-type wheezing episodes, which currently are
not defined as asthma but their risks of having asthma at the
age of 11 is reduced as a result. So this can be argued in many
directions, but the studies from the southern states of America
are quite compelling in that regard.
Professor Hourihane: There is similar data from
Scandinavia about early entry to day-care, which is part of the
social contract in those countries where mothers go back to work
and children go into state-run day-care. The children who go into
state-run day-care before six months, compared to those who go
in after a year or 24 months, have lower rates of asthma and other
allergic conditions. So it is guilt by association. It is very
hard to prove that any particular—I do not know how we would
prove—viral infection in infancy prevented allergy. However,
there are data regarding children who have either been vaccinated
against measles or had wild measles, in Guinea Bissau, and those
who were vaccinated—i.e. they did not have the wild-type
infection—had higher rates of allergies than those who had
had measles and survived it. So it is a trade-off between surviving
measles or not.
Q656 Viscount Simon: The "allergic
march"/progression (whatever you like to call it) describes
the march from mild allergies, such as rhinitis, to more severe
conditions. Is there any particular age at which children typically
are most likely to develop these more serious disorders, and is
there anything that can be done?
Dr Hyer: It depends what you mean by "more
serious". I would say that multiple food allergy in a child
under one or severe eczema which impacts on your growth in a child
under one is, perhaps, more serious than asthma that is looked
after by Mark that is older. I would fight that corner. People
progress through different manifestations of the allergic march
at different rates. For me, the burden of workload is the preschool
child who has multiple food allergy, but as I continue my clinic
as they get older many of them became tolerant to the most significant
foods, which are milk and egg; they may remain allergic for life
to foods such as peanut, which may amount to a serious risk, and
then as I continue running my clinic I inevitably end up running
an asthma clinic or a rhinitis clinic as they get older. People
do progress through symptoms. The preschool child may lose their
original food allergy, but I am not clear that I have a specific
age where the threat is greater. I consider the preschool child
at significant risk.
Professor Harper: I would like to make an important
comment. I do not like the term "allergic march", personally.
I know it is used in the literature a lot but it is often misused;
it is a very loose term and people understand it in different
ways. It seems to me to assume that there is a progression: that
you develop eczema, then you develop your hay fever and then you
develop your rhinitis. I think, these are all individual diseases
which are associated and, perhaps, aggravated by allergy, and
that they vary from one child to another. There is a time difference;
the onset of eczema is primarily in early infancy, under one,
and then perhaps the peak of asthma onset is a bit later and then
the onset of rhinitis after that. However, it is time-related
rather than necessarily a progression in an individual. The ultimate
point here is: is it progressing in such a way that it becomes
more severe? I am not sure that is true. There are genetic factors
as to why some children are born with severe eczema and asthma
and rhinitis, but it is not a progression from one of these disease
entities to another.
Dr Rosenthal: There is a danger of moving from
the particular to the general. There is a very good study from
Cambridge which looked at food allergy events and looked at the
risk of progression to a more severe event subsequently, admittedly
following intervention by training and advice, etc. Certainly
in children the risk of progressing to a more severe event was
virtually zero.
Professor Hourihane: However, it is not the
case that they move from a benign condition of eczema to a more
severe condition of food allergy. Food allergy and eczema are
there in infancy and rhinitis is what develops after several years
of exposure to allergens. The perception that the diseases become
more severe is because the burden of death due to allergies is
in adolescents and teenagers, whose approach or response to their
illness puts them at risk; they ignore the warnings, they take
risks, or they eat in places where they may not be sure of the
provenance or safety of the food. So the severe illnesses start
in childhood and persist, but the responses of individuals to
the conditions may alter their risk through life, as for any other
condition that an adolescent may have to suffer.
Q657 Viscount Simon: It is a common
belief that most children grow out of asthma and allergy, but
am I right in thinking that this may not be true particularly
with regard to food allergies?
Dr Hyer: There are food allergies that persist.
The simple ones that resolve, like cows' milk and the egg, not
all but many children will outgrow. Those with multiple food allergies
sometimes do not and there is a significant burden of children
who have multiple food allergies who are not outgrowing them.
That means that there is a cohort coming through to adulthood,
potentially, who have a one-in-50 chance of having a severe adverse
event were they to face peanut. So in answer to your question,
some of the food allergies you do not outgrow. There is information
still to be gathered—remember, we are seeing a rise in the
prevalence of peanut allergy—but at the moment these ones
seem to persist.
Professor Hourihane: I have been told twice
within a month by two families that they wish their child had
cancer instead of food allergy because there is a cure for cancer.
Q658 Chairman: You commented earlier
on about the absence of the ability possibly to diagnose accurately.
How much do you see that as a problem amongst children and then,
moving on into adulthood, that the actual allergic nature of their
disease has not been adequately diagnosed?
Professor Harper: It is also a perception by
many doctors in different specialities, because this range of
conditions can present to a whole number of different specialities
and they each have different protocols of management. It all needs
to be much more co-ordinated, with a greater awareness for potentially
aggravating factors, whether it is eczema or asthma and so on,
and to investigate allergy. That is what is important, and to
be able to have the facilities to be able to do that. There is
a need for awareness right up from general practice to specialist.
Q659 Lord Colwyn: Would children
stand a greater chance of outgrowing an allergy if they were on
a totally restrictive diet which prevented any taking-in of that
food? Or would they stand more chance of outgrowing it if they
carried on eating it and slowly acclimatised themselves to it?
Dr Hyer: A wonderful question and there will
be many different answers to that. We know that in terms of primary
prevention the best tool is to breast feed. Breast feeding is
not a mechanism by which you are not exposed to allergens; you
are exposed to hundreds—thousands. The advice of the Department
of Health, for example—and this is particularly controversial
and will cause much concern—about not having peanuts to
eat in the first three years of life if you are at risk may not
be what happens in the rest of the world. So when you compare
that with data in Israel where the prevalence of peanut allergy
is so low, is it because they are weaned on to sweets and crisps
that contain peanut? We do not really know the answer to that,
and this is being addressed by studies which are funded studies
at the moment. We know that breast feeding helps. We know that
if you have severe eczema you may benefit by going on to a hypoallergenic
feed when weaned and not being fed cow's milk formula, but because
of the diagnostic difficulties that you so kindly mention, selecting
which patient should take on which avoidance pattern is very complicated
and sometimes managed in general practice but really ought to
be managed at a specialist level, whether it be at an allergist
level or an organic-specific consultant who can take on that question.
It is very complicated and very individual because the diagnostic
test difficulties that you have alluded to requires judgment which
is not available in general practice.
Professor Hourihane: I would rarely put children
on total elimination diets. I would say it happens, maybe, once
every year to eighteen months. There are other ways. The major
allergic manifestation is usually eczema under the age of one
and failure to thrive with gastro-intestinal symptoms. So an integrated
approach and the holistic management of these things is the key.
Elimination can be appropriate but it is extremely limiting on
the family; it makes the child unadventurous in new situations,
socially isolated and it should not be undertaken except under
specialist care. So we are not in favour of such elimination diets
being started in primary care before being assessed by an allergist,
because, for one thing, they may be nutritionally unsound unless
they are properly supervised and they may be promoted or persisted
with for far too long after the allergy has gone away. As we have
heard, milk and egg allergy go away in the first four or five
years of life. I am encountering now, in Ireland, where there
is an even less developed allergy service than in the UK, children
of nine or 10 who are still on elimination diets for a reaction
that they had in the first year of life. Their social wherewithal
is very limited.
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