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An allergy or Type I hypersensitivity is an immune system
malfunction whereby a person's body is hypersensitised to
react immunologically to typically nonimmunogenic
substances. When a person is hypersensitised, these
substances are known as allergens. The word allergy derives
from the Greek words allos meaning "other" and ergon meaning
"reaction" or "reactivity". Type I hypersensitivity is
characterised by excessive activation of mast cells by
immunoglobulin E resulting in a systemic inflammatory
response that can result in symptoms as benign as a runny
nose, to life-threatening anaphylactic shock and death.
History
The term and concept of "allergy" was coined by a Viennese
pediatrician named Clemens von Pirquet in 1906 [1]. He
observed that the symptoms of some of his patients might
have been a response to outside allergens such as dust,
pollen, or certain foods. For a long time all
hypersensitivities were thought to stem from the improper
action of inflammatory immunoglobulin class IgE, however it
soon became clear that several different mechanisms
utilizing different effector molecules were responsible for
the myriad of disorders previously classified as
"allergies". A new four-class (now five) classification
scheme was designed by P. G. H. Gell and R. R. A. Coombs.
Allergy has since been kept as the name for Type I
Hypersensitivity, characterised by classical IgE mediation
of effects.
Signs and symptoms
Allergy is characterised by
a local or systemic inflammatory response to allergens.
Local symptoms are:
-
Nose: swelling of the nasal
mucosa (allergic rhinitis)
- The distinctive behavior
known as nasal salute, also known as allergy
salute, is the habit of wiping of the nose in an
upward direction due to itching.
-
Eyes: redness and itching of
the conjunctiva (allergic conjunctivitis)
-
Airways: bronchoconstriction,
wheezing and dyspnoea, sometimes outright attacks of
asthma
-
Skin: various rashes, such as
eczema, hives (urticaria) and contact dermatitis.
Systemic allergic response is
also called anaphylaxis. Depending of the rate of severity,
it can cause cutaneous reactions, bronchoconstriction,
edema, hypotension, coma and even death.
Hay fever is one example of an exceedingly common minor
allergy - large percentages of the population suffer from
hayfever symptoms in response to airborne pollen. Asthmatics
are often allergic to dust mites. Apart from ambient
allergens, allergic reactions can be due to medications.
Diagnosis
There are several methods
for the diagnosis and assessment of allergies.
Skin test
The typical and most simple
method of diagnosis and monitoring of Type I
Hypersensitivity is by skin testing, also known as prick
testing, due to the series of pricks made into the patient's
skin. Small amounts of suspected allergens and/or their
extracts (pollen, grass, mite proteins, peanut extract,
etc.) are introduced to sites on the skin marked with pen or
dye (the ink/dye should be carefully selected, lest it cause
an allergic response itself). The allergens are either
injected intradermally or into small scratchings made into
the patient's skin, often with a lancet. Common areas for
testing include the inside forearm and back. If the patient
is allergic to the substance, then a visible inflammatory
reaction will usually occur within 30 minutes. This response
will range from slight reddening of the skin to full-blown
hives in extremely sensitive patients.
After performing the skin test and
receiving results, the doctor may apply a steroid cream to
the test area to reduce discomfort (such as itching and
inflammation).
Problems with skin test
While the skin test is
probably the most preferred means of testing because of its
simplicity and economics, it is not without complications.
Some people may display a delayed-type hypersensitivity (DTH)
reaction which can occur as far as 6 hours after application
of the allergen and last up to 24 hours. This can also cause
serious long-lasting tissue damage to the affected area.
Fortunately, these type of serious reactions are quite rare.
In addition, the application
of previously unencountered allergens can actually sensitize
certain individuals to the allergen; that is, cause the
inception of a new allergy in susceptible individuals.
Skins tests also are not
always able to pinpoint a patient's specific allergies if
the patient has an allergy but does not react to the skin
test allergen.
Total IgE count
Another method used to qualify type I
hypersensitivity is measuring the amount of serum IgE
contained within the patient's serum. This can be determined
through the use of radiometric and colormetric immunoassays.
Even the levels the amount of IgE specific to certain
allergens can be measured through use of the
radioallergosorbent test (RAST).
Treatment
There are limited mainstream
medical treatments for allergies. Probably the most
important factor in rehabilitation is the removal of sources
of allergens from the home environment, and avoiding
environments in which contact with allergens is likely. The
trouble with them is that they have not all been proven.
Therefore it could be seen as a
placebo; however, it has helped people.
Immunotherapy
Hyposensitization is a form of immunotherapy
where the patient is gradually vaccinated against
progressively larger doses of the allergen in question. This
can either reduce the severity or eliminate hypersensitivity
altogether. It relies on the progressive skewing of IgG
("the blocking antibody") production, as opposed to the
excessive IgE production seen in hypersensitivity type I
cases.
In the
1960s, Dr. Len McEwen in the United Kingdom developed a
treatment for allergies known as enzyme potentiated
desensitization, or EPD. EPD uses much lower doses of
antigens than conventional treatment, with the addition of
an enzyme. EPD is available in the United Kingdom and
Canada, and was available in the United States until 2001,
when the Food and Drug Administration revoked its approval
for an investigative study being performed. Since that time
an American counterpart to EPD, known as Low Dose Antigens,
or LDA, has been formulated from components approved by the
FDA, and is available for treatment from a small number of
doctors in the United States. EPD (and LDA) is still
considered experimental by many mainstream doctors and
medical insurance companies, and many doubt that it is more
effective than a placebo.
A third form of immunotherapy involves the intravenous
injection of monoclonal anti-IgE antibodies. These bind to
free and B-cell IgE signalling such sources for destruction.
They do not bind to IgE already bound to the Fc receptor on
basophils and mast cells as this would stimulate the
allergic inflammatory response.
Chemotherapy
Several antagonistic drugs are used to
block the action of allergic mediators, preventing
activation of cells and degranulation processes. They
include antihistamines, cortisone, adrenalin (epinephrine),
theophylline and Cromolyn sodium. These drugs help alleviate
the symptoms of allergy but play little role in chronic
alleviation of the disorder. They can play an imperative
role in the acute recovery of someone suffering from
anaphylaxis (which is why those allergic to bee stings,
peanuts, nuts, and shellfish often carry an adrenalin needle
with them at all times).
Alternative therapies
In alternative medicine, a number of
treatment modalities are considered effective by its
practitioners in the treatment of allergies, particularly
homeopathy, traditional Chinese medicine and kinesiology.
However, none of these have been backed up by good quality
evidence. On the contrary, they are generally criticised by
mainstream medical researchers to be supported only by
anecdotes, which makes them effective only as placebos. Yet
there are case studies involving animals and babies, which
makes it diffcult to categorise all such successful
treatment as being the result of placebos.
Pathophysiology
All hypersensitivities
result from an aberration somewhere in the normal immune
process. The exact cause of such malfunctions is not always
apparent, however, and several arguments from genetic-basis,
environmental-basis and intermediate proponents exist with
varying validity and acceptance.
Acute response
The difference between a type I
hypersensitivity reaction against an allergen to the normal
humoral response against a foreign body is that plasma cells
secrete IgE as opposed to either IgM (against novel
antigens) or IgG (against immunized antigens). IgE binds to
Fc receptors on the surface of mast cells and basophils,
both involved in the acute inflammatory response.
When IgE is first secreted it binds to the
Fc receptors on a mast cell or basophil, and such a IgE-coated
cell is said to be sensitized to the allergen in question. A
later exposure by the same allergen causes reactivation of
these IgE, which then signal for the degranulation of the
sensitized mast cell or basophil. These granules release
histamine and other inflammatory chemical mediators
(cytokines, interleukins, leukotrienes, and prostaglandins)
into the surrounding tissue causing several systemic
effects, such as vasodilation, mucous secretion, nerve
stimulation and smooth muscle contraction. This results in
the previously described symptoms of rhinorrhea, itchiness,
dyspnea, and anaphylaxis. Depending on the individual,
allergen, and mode of introduction, the symptoms can be
system-wide (calliscal anaphylaxis), or localised to
particular body systems (for example, asthma to the
respiratory system; eczema to the dermis).
Late-phase response
After the chemical mediators of the acute
response subside, late phase responses can often occur. This
is due to the migration of other leukocytes such as
neutrophils, lymphocytes, eosinophils and macrophages to the
initial site. The reaction is usually seen 4-6 hours after
the original reaction and can last from 1-2 days. Cytokines
from mast cells may also play a role in the persitence of
long-term effects. Late phase responses seen in asthma are
slightly different to those seen in other allergic
responses.
Basis of the allergic
response
Genetic Basis
There is much evidence to
support the genetic basis of allergy, as allergic parents
are more likely to have allergic children, and their
allergies are likely to be stronger than those from
non-allergic parents. However some allergies are not
consistent along genealogies with parents being allergic to
peanuts, but having children allergic to ragweed, or
siblings not sharing the same allergens. Ethnicity has also
been shown to play a role in some allergies. Interestingly,
in regard to asthma, it has been suggested that different
genetic loci are responsible for asthma in people of
Caucasian, Hispanic, and African origins.
Relationship with parasites
Some recent research has also begun to
show that some kinds of common parasites, such as intestinal
worms (e.g. hookworms), secrete immunosuppressant chemicals
into the gut wall and hence the bloodstream which prevent
the body from attacking the parasite. This gives rise to a
new slant on the "hygiene hypothesis" - that co-evolution of
man and parasites has in the past led to an immune system
that only functions correctly in the presence of the
parasites. Without them, the immune system becomes
unbalanced and oversensitive. Gutworms and similar parasites
are present in untreated drinking water in undeveloped
countries, and in developed countries until the routine
chlorination and purification of drinking water supplies.
This also coincides with the time period in which a
significant rise in allergies has been observed. So far,
there is only sporadic evidence to support this hypothesis -
one scientist who suffered from seasonal allergic rhinitis (hayfever)
infected himself with gutworms and was immediately 'cured'
of his allergy with no other ill effects. Full clinical
trials have yet to be performed however. It may be that the
term 'parasite' could turn out to be inappropriate, and in
fact a hitherto unsuspected symbiosis is at work.
Basis of increasing
prevalence
There has been a notable
increase in the commonness of allergies in the past decades,
and there are multiple hypotheses explaining this
phenomenon. This is in part because we know what they are,
in contrast to earlier humans who would think that it is a
non-important illness.
The hygiene hypothesis
One theory that has been
gaining strength is the "hygiene hypothesis". This theory
maintains that since children in more affluent countries are
leading a cleaner and cleaner life (less exposure to dirt,
extra use of disinfectants, etc), their immune systems have
less exposure to parasites and other pathogens than children
in other countries or in decades past. Their immune systems
may, therefore, have many "loaded guns", cells which might
have targeted, say, the intestinal worms that no longer
cause trouble in affluent neighbourhoods. Having no
reasonable target, these cells inadvertently become
activated by environmental antigens that might only cause
minor reactions in others. It is the symptoms of this
exaggerated response that is seen as the allergic reaction.
Many common allergies such as asthma have seen huge
increases in the years since the second world war, and many
studies appear to show a correlation between this and the
increasingly affluent and clean lifestyles in the West. This
is supported by studies in less developed countries that do
not enjoy western levels of cleanliness, and similarly do
not show western levels of incidences of asthma and other
allergies. During this same period, air quality, at one time
considered the "obvious" cause of asthma, has shown a
considerable improvement. This has led some researchers to
conclude that it is our "too clean" upbringing that is to
blame for the lack of immune system stimulation in early
childhood.
So far the evidence to
support this theory is limited.
Increasing use of chemicals
Another theory is the
exponential use and abuse of chemicals in affluent nations
since the second world war. Vast numbers of chemicals are
introduced into our indoor and outdoor environments with
little or no testing regarding their toxicity to living
beings. Many believe that air quality is getting worse
rather than better, particularly if one considers indoor air
quality as well as outdoor. (Indoor air quality has become
significantly worse since building codes changed in the
1970s to make buildings more air-tight to conserve energy.
This affects buildings built since that time.) Adverse
reactions to toxins vary considerably from one person to
another, and can involve extremes in symptoms including the
neurological and endocrine systems as well as the more
commonly recognized allergy symptoms listed above.
In 2004, a joint Swedish-Danish research team (Bornehag et
al.) found a very strong link between allergies in children
and the phthalates DEHP and BBzP, commonly used in PVC.
Allergies are also viewed by some medical practitioners as a
negative consequence of the use and abuse of antibiotics and
vaccinations. This mainstream Western approach to treatment
and prevention of infectious disease has been used in the
more affluent world for a longer period of time than in the
rest of the world, hence the much greater commonality of
allergies there. It is hypothesized that use of antibiotics
and vaccination affect the immune system, and that allergies
are a dysfunctional immune response. There is, however, very
little evidence to support this view.
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