Memorandum by the Immunology SAC, Royal
College of Pathologists
Immunologists and allergists provide specialist
clinical allergy services in the UK, and are the only medical
specialties with extensive training in the immunological basis
of allergy and the clinical care of patients with allergic disorders
affecting all organ systems. Allergists devote all their professional
time to the management of Allergy, immunologists often have other
responsibilities and varied job plans, but most devote substantial
parts of their professional time to the provision of allergy services.
The remit of the House of Lords Sub-Committee
is very wide-ranging and will require a thorough review of a vast
amount of evidence. The published evidence on conventional practice,
and that on complementary therapies will need to be subjected
to proper scrutiny for quality, lack of methodological flaws,
exclusion of placebo effect and reproducibility before being used
as evidence for public policy decision-making.
1. DEFINING THE
PROBLEM
1.1 What is allergy? What is the difference
between allergy and intolerance?
1.1.1 Allergy—Immunological disease
mediated by the Immune system—it has a limited number of
stereotypic manifestations which are dictated by the immunological
mechanisms underlying Mast cell activation. It has a genetic basis,
but the expression of disease is influenced by the environment
and reproducible allergen-triggered, IgE antibody-mediated disease
mechanisms can be identified and give rise to clinically disease.
1.1.2 Intolerance is a catch-all term for
any adverse effect experienced by an individual which is often
mistakenly attributed to allergy but for which there is no reputable
evidence to suggest that it is an immunological adverse reaction
to foods or medicines. Some "intolerances" such as food-induced
migraine are probably pharmacological actions of the food. Intolerance
is therefore a state of sensitivity to a specific environmental
component which manifests within an individual, objectively or
subjectively, as a reproducible unpleasant reaction upon exposure
to that component.
1.1.3 Detailed nomenclature can be found
at http://www.eaaci.net/site/nomenclature.pdf.
1.1.4 Much information including practice
parameters/position statements and expert evidence-based guidelines
on the management of allergic disease can be found at the websites
of allergy/Immunology professional societies such as www.BSACI.org.uk;
www.aaaai.org; www.eaaci.net.
1.2 Why is the incidence of allergy and allergic
diseases rising? Why does the UK in particular have such high
prevalence of allergy?
1.2.1 The incidence of many forms of allergy
is clearly rising and the rise does not appear to be related to
better reporting and diagnosis, but the reasons are poorly understood.
Epidemiological meta-analysis of the existing data has already
been published as an appendix to the DH (Department of Health)
report into the provision of allergy services, but caution is
needed in comparison of results in different countries. The lack
of systematic meta-analysis is hampered by the variable quality
of the data and expert large scale epidemiological studies are
required—the UK is uniquely well-placed to deliver these
studies through the NHS and associated research but the lack of
investment in the future training of specialists practicing allergy
and immunology and the difficulties pursuing an academic medical
career (likely to result from a potential reduction in overall
funding associated with the Culyer report) are likely to impair
this important work.
1.2.2 It is not known why the UK or anywhere
else has a rising incidence of allergic disease—although
there are many hypotheses all of which remain unproven. Despite
their plausibility, the link is still speculative for most. The
DH review highlighted the gaps in evidence at present.
1.3 What is and what is not known about the
origins and progression of allergic disease?
1.3.1 There is much work still to be done
on the genetic and environmental predisposition to the development
of allergic disease, and strategies to prevent its development
or modify its expression in individuals. In the absence of a national
strategy, the failure to support and develop academic and NHS
research into allergic disease may seriously impair future understanding
of the issues in the UK. There is exciting and preliminary work
suggesting that the "Allergic March" in children can
be prevented by early immunotherapeutic intervention.
1.3.2 What is known:
— Genetic influences (some of).
— Environmental influences (some of).
— Immuno(dys)regulatory mechanisms
(some of).
— Intrauterine and postpartum influences
(some).
— The existence of the "allergy
march".
— Age influences on disease presentation.
1.3.3 What is not known: [Sic]
— Why predominance of different clinical
presentations at different ages?
— Why does some atopy manifest as clinical
disease and some remain latent?
— What factors determine mild vs. moderate
vs. severe allergy.
— How to predict the severity of the
next reaction in an individual in order to tailor individual treatment
plans and risk-assessments.
— How to prevent allergy developing
or modify its severity.
— There are many putative factors with
varying levels of supporting evidence.
— Hygiene hypothesis (much conflicting
evidence).
— Pollution (personal and environmental).
— Lifestyle effects (homes, pets, diet
etc).
— Climate—effects on home environment—eg
for House dust mite.
1.4 What gaps exist in establishing the overall
disease burden for all types of allergy and what are the barriers
to filling these gaps?
1.4.1 Evidence has delineated a substantial
and underestimated disease burden in the UK. Further work is needed
to develop robust evidence base with validated measures, this
is unlikely to occur if the specialities of Allergy and Immunology
are not developed as part of a national strategy to improve NHS
service and research provision, as well as providing the infrastructure
for the proper gathering of such information.
1.4.2 There are likely to be significant
gaps in robust mechanisms for workload recording/capacity in primary
care and secondary/tertiary care. These will be essential for
teasing out allergy workloads from workload recording of related/overlap
diseases—especially in Immunology centres as opposed to
pure Allergy centres. Improved coding necessary to collect this
information in a sophisticated and standardised way is essential,
as current ICD 10 and Payment by results codes are currently insufficiently
detailed. It is hoped that NHS data collection will gradually
be improved by these drivers.
1.4.3 There are many barriers which need
to be overcome—recognition at local/commissioning level
that allergy is a significant problem for the NHS, improved allocation/prioritisation
of resource for allergy research, and successful establishment
of the relevant NHS IT infrastructure to support improved data
collection which is currently underway.
1.5 In addition to the impact on the health
service, what is the overall socio-economic impact of allergic
diseases (for example, absence from work and schools)?
1.5.1 The assessment of disease burden or
socio-economic impact with any reliability is also very difficult,
and difficulties in validation of presumed measures of economic
impact. It is clear however from the evidence presented to the
DH Review, and evidence from patients, patient support organisations,
allergists, immunologists, GPs, nurses and other medical specialties,
that allergy in all its forms has considerable impact on the lives
of patients, disrupting schooling, work, and general quality of
life, as well as the risk of death and other morbidity from more
serious forms of allergy and asthma.
TREATMENT AND
MANAGEMENT
2.1 What is the effect of current treatments
on the natural history of allergic disease?
2.1.1 There is much published evidence for
the effectiveness of interventions by allergists/immunologists
(see AAAAI "Consultation and referral guidelines citing the
evidence: How the allergist-immunologist can help"—on
www.aaaai.org) particularly for allergen avoidance strategies,
immunotherapy and treatment of asthma, hay fever and specific
food allergies. A review of meta-analysis of effectiveness of
treatments has been published as an appendix to the DH report.
This highlighted the need for more research and gaps in the evidence.
This will require the support and development of national centres
of expertise, a network of regional centres of excellence in NHS
service provision (primarily through allergists and immunologists
and multidisciplinary team working) and improved service provision
and data collection in primary care. Much of NHS treatment in
all specialties is of necessity based on expert opinion and experience
in the absence of randomised double-blind controlled trials in
many areas. While we all strive to correct this, and NICE may
be given the task of reviewing evidence to identify interventions
for which there is evidence of ineffectiveness (in a limited number
of interventions, not involving allergy to date). The select committee
must remember that lack of evidence of effectiveness is not
evidence of lack of effectiveness. The two are often conflated
in policy decision-making, often erroneously.
2.1.2 Pharmacotherapeutic options currently
available are unlikely to have significant effects on natural
history of disease other than primarily managing symptoms. The
same may well be true for allergen avoidance/environmental modification
measures.
2.2 The data on complementary interventions
2.2.1 Research into complementary interventions
is inadequate and this is a highly contentious issue. While acknowledging
that the evidence base for many conventional treatments is sub-optimal,
this should not influence the critical scientific evaluation of
the quality of evidence for complementary interventions, which
is often regarded as poor by most scientific standards.
2.2.2 To our knowledge there is only one
chair of Complementary Medicine in the UK (at the Peninsular Medical
School in Plymouth ( http://www.pms.ac.uk/compmed).
2.2.3 "Vega" testing has recently
been examined as complementary diagnostic technique without demonstrating
efficacy (Lewith et al BMJ 2001;322:131-134 ). Interventional
studies are often flawed and difficult to interpret due to methodological
biases.
2.2.4 If necessary the committee should
consider clearly argued critiques of the evidence for the more
esoteric complementary therapies from a "conventional"
medical/scientific standpoint, as well as the counter arguments
of the proponents of esoteric therapies to gain an insight into
the controversial nature of these debates.
2.2.5 The committee should familiarize themselves
with the position statements on complementary therapies of the
RCP (Royal College of Physicians), AAAAI, BSACI (including that
submitted to the DH review) and other allergy and immunology organisations
for the expert consensus view of the evidence for some complementary
therapies.
2.2.6 Most conventional medical practitioners
and professional societies have reservations about the quality
of evidence for many complimentary investigations and acknowledge
the difficulty in producing interventional studies of sufficient
power which are not subject to error and biases or the placebo
effect (even if the placebo effect is a very important tool in
making patients feel better and an important part of patient care,
even in conventional medicine).
2.2.7 There is some recently published data
of doubtful validity to suggest that IgG antibodies may predict
food intolerances but this is controversial and is not confirmed
by other studies. Interventional studies using dietary avoidance
may have methodological errors that may lead to biases which make
them unreliable.
2.3 Evidence base for Pharmacological and
non-pharmacological Management Strategies
2.3.1 To a certain extent the evidence base
has been examined in the appendices to the DH review. This is
far too large an area to review in this submission but we would
direct the select committee to the evidence submitted to the DH
enquiry by the BSACI and others, and to the websites above, for
expert consensus opinion.
2.3.2 The evidence base for most standard
pharmacotherapeutic options—corticosteroids, H1blockers
etc. have a significant body of evidence underpinning their beneficial
use in allergy.
2.3.3 Adrenaline in anaphylaxis—Expert
opinion and extrapolation from retrospective observations, including
the UK Rescusitation Council Guidelines agree about the likely
benefits, but objective evidence is lacking because of the obvious
difficulties which preclude the studying of its efficacy in randomised
controlled trials. It would be unethical not to administer adrenaline
to a patient with anaphylaxis. There is also the distinction between
the end-points of efficacy for prevention of fatalities and efficacy
in rapidly terminating an episode and reducing morbidity which
must be considered. This is a good example of lack of evidence
of efficacy not being equated with evidence of lack of efficacy.
2.3.4 Anti-IgE—There is evidence of
efficacy in severe asthma, and in increasing the dose tolerance
of patients with food allergy, and it may have a role in other
allergic disorders. Its place in routine practice in the UK is,
as yet, unclear although there is much potential in other areas
of allergy practice.
2.3.5 Non-pharmacological: Allergen avoidance:
Once again there are difficulties in interpreting the existing
evidence. Intuitively this is a "common sense" measure
which ought to be highly effective, and there is data to demonstrate
this in some food allergies such as peanut sensitivity. Objective
evidence of efficacy in most sorts of aeroallergen allergy eg
House Dust Mite Sensitivity is difficult to obtain, most likely
due to a lack of comparability between different studies because
of methods and patient selection.
2.4 Is the level of UK research into allergy
and allergic disease adequate?
2.4.1 Clearly not, even though much excellent
research is done by a small cadre of specialists—see appendices
to DH Review July 2006 and comments above. More importantly, there
is reason to believe that the future of such clinically-based
applied/translational research is precarious in view of the small
number of specialists and lack of training opportunities.
2.4.2 Both specialties lack manpower and
have insufficient training posts, leading to current and future
difficulty with recruitment and retention of clinical and academic
specialists. A strategy is required to facilitate effective NHS
research into the cost-effectiveness of different methods of service
delivery and advance the treatment and understanding of allergic
disease in general. These two aspects (service provision and research
strategy) cannot be easily divorced in a highly specialised clinical
service area with a small workforce.
2.4.3 Answers to UK specific problems will
not be forthcoming without support for the retention and development
of a cadre of specialist allergists/immunologists, and results
from other countries may not always be relevant to a UK population.
2.5 What are the most promising areas of research
into preventing or treating allergy?
2.5.1 There are many promising interventions
including:
— Conventional allergen desensitization.
— New forms of immunotherapy with T
cell modulating allergens, modified allergens and use of anti-IgE
antibody therapy outside of asthma.
— Different routes of administration
such as sublingual immunotherapy.
— Use of conventional allergen immunotherapy
in children to prevent the development of asthma is promising.
— Bradykinin- and tryptase-inhibiting
drugs and other potentially useful interventions are in development.
— Many of these experimental interventions
have been championed by UK researchers and clinicians and the
continuation of this in the future is in jeopardy without a coherent
strategy to secure specialised services and consequent clinical
applied research and development.
2.5.2 There is also a need for research
into:
— Service delivery/deficiencies/needs/gaps
issues.
— Efficacy of models of patient/profession
education.
— The natural history of food allergy
is poorly understood although we have some preliminary understanding.
We suspect that some people with nut allergy outgrow their sensitivity
with time but cannot predict who will do so. We also do not know
if these people have a risk of re-sensitisation. There are more
questions than answers at the present time.
3. GOVERNMENT
POLICY
3.1 How is current knowledge about the causes
and management of allergic disease shared within Government?
3.1.1 We are not aware of effective sharing
of knowledge or appropriate input into government policy in these
areas other than the DH review and select committee report, although
professional societies, patient support groups and Royal Colleges
all responded to consultations and reviews when asked. This is
a situation that has been of concern to the Royal College of Pathologists
for some time in many areas of governmental activity, and it is
clear that decision-making will be much improved with effective
stakeholder and expert input. A mechanism is needed to facilitate
this. There exists a body of experts in the Royal Colleges, willing
and able to assist in the formulation of government policy yet
often there appears to be no mechanism for ensuring that this
resource is effectively and routinely tapped. The Royal College
of Pathologists keen to act as a resource for identifying individuals
with the appropriate expertise in any given area.
3.2 How effective have existing Government
policy and advice been in addressing the rise in allergies?
3.2.1 The committee is not aware of any
evidence of such action or evidence of its effectiveness. Part
of the problem lies in a lack of suitable evidence in relevant
areas, for example into allergen avoidance strategies for infants
to potentially reduce the incidence of food sensitisation.
3.2.2 We feel that government policy to
date has not been effective in addressing the needs of patients
with allergy. The DH concluded that there was a considerable burden
of allergic disease, that more specialists were required, and
that provision of services was inadequate and geographically unequal
and needed to be addressed, perhaps by networking. The report
of the DH Select Committee did highlight the need for a network
of allergy services throughout the UK, the need for additional
training positions and the need for expert review of the effectiveness
of interventions perhaps through NICE. Unfortunately to date there
is no obvious mechanism or driver to achieve this.
3.2.3 One key problem in allergy is how
to engage local health commissioners to prioritise the establishment
of adequate local allergy services in the face of all the other
centrally driven demands on their budgets, such as the Quality
and Outcomes frameworks for General Practice and Cancer and Heart
Diseases National service frameworks, NICE guidance and other
drivers. Care and education of patients with allergic disease
and continued NHS research and development of new treatments and
interventions is unlikely to improve significantly in the absence
of such a driver.
3.3 Do housing policy and regulations governing
the indoor environment pay enough attention to allergy?
3.3.1 We are not aware of evidence that
housing policy can impact on allergy development or treatment
unless it is proven that a patient is sensitive to a controllable
environmental allergen such as mould spores or dust-mite. This
may be of more relevance to work environments where we believe
that protection against the development of occupational allergy
is often covered by Health and Safety legislation.
3.4 How effectively are food policy and food
labelling regulations responding to the rise in food allergies?
3.4.1 Food labelling is very important—some
clear steps have been taken to make labelling mandatory including
FSA documents but much more action needed (see http://www.food.gov.uk/safereating/allergyintol).
The FSA 2002 report "Adverse reactions to food and food ingredients"
has already examined some of the issues on this topic). One major
difficulty is knowing what the minimum threshold for labelling
should be, and how to risk-assess this—a few individuals
could potentially be sensitive to trace amounts of rare allergens,
others may not. This is a difficult issue requiring much careful
thought. The role or risks/benefits of genetically modified foods
is essentially unknown.
3.4.2 While food allergy must be taken seriously,
some express concerns that an inappropriately low threshold for
use of hazard warnings may be problematic. This problem impacts
on patients who regularly report difficulties with selecting allergen-free
foods and complicates the interpretation of supermarket labelling—where
foods which are apparently very unlikely to contain an allergen
are labelled as a risk, but the assessment of the level of risk
is unclear. Some evidence based consistency and guidance is required.
PATIENT AND
CONSUMER ISSUES
4.1 What impact do allergies have on the quality
of life of those experiencing allergic disease and their families?
4.1.1 There is much supporting evidence
demonstrating that quality of life is impaired by every type of
allergy from rhinitis to food-related anaphylaxis, and that allergy
impacts adversely on many aspects of daily living. This may be
addressed by better services support and advice in primary care,
probably best supported by specialist hospital centres with extensive
and up-to-date expertise. Much of this work is provided by patients
support agencies and charities in the absence of easy access to
expert consultations with allergist or immunologists.
4.1.2 There is preliminary evidence that
management by an expert team is of benefit and improves patient
outcomes but more work is required.
4.2 What can be done to better educate the
public and to improve the quality of information that is available
to patients and undiagnosed sufferers?
4.2.1 A lot could be done to improve availability
of information and advice from professional as well as informed
lay organisations, but much allergy advice requires to be individualized
and the construction of appropriate local information is dependent
on local medical expertise in allergy which is scarce.
4.2.2 Allergy and immunology centres provide
extensive patient support. This includes information, training
in the use of rescue medication and expert assessment of the patients'
individual needs. A recent publication in the BMJ suggested that
EpipensTM were oversubscribed such that the putative cost of each
putative life saved was 20 million pounds, however this point
of view is flawed because it ignores the benefits of proper treatment
plan in managing anxiety, preventing morbidity and reducing symptoms.
Expert risk-assessment and research into improved prognostic markers
by expert units is required in order to minimise this cost to
the NHS and ensure that rescue medications and therapy are administered
in a cost-effective and clinically appropriate manner. It is unlikely
that we can rely on non-expert assessment in primary care without
clear national evidence-based guidelines which will need to be
supported through a local expert allergist/immunologist.
4.2.3 Nationally, a lead needs to be taken
by allergist/immunologists, to create national service standards,
create a workable network of NHS allergy services with clear referral
patterns and community outreach—including support for education
and training in primary care.
4.2.4 Web-based guidance and information—often
including that of some patient support groups—is not quality-assured
and often mix complementary approaches and conventional advice,
which can lead to confusion.
4.3 Are current regulatory arrangements, for
example, those governing private clinics offering diagnostic and
therapeutic services and the sale of over the counter allergy
tests, satisfactory?
4.3.1 Regulation of non-NHS clinics and
over-the-counter treatments for allergy is not adequate—extensive
evidence that it leads to direct harm to individuals is lacking,
but there is clearly a legitimate concern that ineffective or
misleading advice may be harmful, costly and may divert patients
from effective evidence-based interventions. High street stores
or private centers may offer complementary diagnostic testing
with unproven techniques.
4.3.2 POCT (point-of-care-testing or near-patient
testing) is a major potential problem even with conventional evidence-based
assays when offered in a context of inadequate quality assurance
procedures, and by staff who do not have the clinical training
or expertise to properly interpret their significance. A specific
IgE test which is offered without evidence-based expert assessment
of the pre-test probability of allergic disease is worthless and
potentially misleading. This is potentially as great a problem
as that of the use of un-validated complementary tests of doubtful
value. A positive test is not the same as the presence of a clinically
important allergy or vice versa. We do not feel that a policy
of "caveat emptor" is appropriate in health policy where
there is an effective evidence-based conventional intervention,
or where it may lead to harm, and feel that a proper regulatory
framework is required.
4.3.3 Hospital laboratories offering diagnostic
allergy tests are required to submit to a regime of inspection
against quality standards in order to be able to offer NHS diagnostic
services. The same must apply to other providers and the government
should assemble an equivalent policy on the basis of an expert
review of the evidence.
9 October 2006
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