Posts Tagged ‘challenge test’

The simplest and most certain test for any sensitivity reaction is to expose the person concerned to the substance under suspicion and see what happens. This is known as a

challenge test. With true allergies, challenge tests are powerful tools, but they are also alarmingly close to reality. The risk of provoking a severe reaction requires a very

cautious approach.
By comparison, an indirect test – a roundabout way of seeing how the body responds, such as the skin-prick test (see p. 91) – has the advantage of rarely producing dangerous

reactions. The downside is that indirect tests can be misleading, precisely because they are not like the real-life situation. No indirect test is perfect – there are always

false positives and false negatives (see box on p. 91).
Challenge tests
If you undergo a challenge test with food or an airborne allergen, you will also be given dummy challenges with an innocuous substance which is indistinguishable from the item

being tested. Neither you, nor the tester who is scoring the reaction, should know which is which. This is called a double-blind trial because, to eliminate all possible bias,

both of you are in the dark. (The full name is a ‘double-blind placebo-controlled trial’ – the dummy challenge is also called a ‘placebo challenge’ or ‘control challenge’.)
The double-blind trial is a standard medical procedure and does not imply that the doctors think you are faking symptoms. Psychological forces are powerful things, and just

thinking that you might react to a test can be enough to produce a reaction – the process that generates the symptoms is largely unconscious.
Food challenge
A food challenge – eating the food that is under suspicion – is a key test for food intolerance (see p. 197). It is sometimes used for food allergy and other forms of food

sensitivity too, as a follow-up to skin tests. Some allergists use a food challenge only if the skin test is at odds with actual events reported by the patient. Other allergists

use food challenge more readily, to confirm skin-test results, and to assess the severity of the reaction.
Extreme caution must be exercised with immediate food allergy, because of the considerable risks involved. The test must be done under medical supervision with resuscitation

equipment to hand. A challenge test should never be done for true food allergy without some careful preliminary tests on the face and the lips (see box on p. 23). Even if these

tests produce no reaction, only tiny amounts of the food should be eaten to begin with.
Bronchial challenge
This type of test involves inhalation of an airborne allergen – such as pollen – suspected of causing asthma. Bronchial challenge carries the risk of provoking a severe asthma

attack, and few doctors use it unless there are compelling reasons to do so – such as demonstrating that someone’s asthma is due to an allergen encountered at work.
Skin-prick tests
This is an indirect method of detecting true allergic reactions. It is one of a family of skin tests that use a similar approach. The three different tests in this family are

known as: skin-prick tests or prick tests, puncture tests, and scratch tests.
For the skin-prick test – the technique used in Britain – a small drop of liquid containing an allergen, such as grass pollen, is placed on the arm. The doctor makes a small

prick in the skin, under the drop of liquid, allowing a minuscule amount of the allergen to get into the skin. A positive reaction is recorded if a red bump develops soon

afterwards. For accuracy, the bump must be compared to positive and negative controls (see below).
The puncture method is very similar to the skin-prick test but uses a slightly different technique for breaking the skin. The term prick-puncture test covers both techniques.
With the scratch method, the skin is scratched lightly, and the allergen solution is then applied over the scratch. This method gives less consistent results than prick-puncture

testing.
It is important to include a negative control in the test – a skin-prick test with plain salt water (saline). This should not produce much of a bump – if it does, the skin is

clearly over-reactive and the tests more difficult to assess. The doctor should also include a positive control – a skin-prick test with histamine, the substance that plays a

central role in allergic reactions. This should always produce a bump. If it does not, the skin is decidedly under-reactive, and the tests are invalid.
Taking antihistamines will make the skin under-reactive, and you should stop taking them before the testing, for a period ranging from a day to several weeks – it varies

depending on the particular antihistamine. Ask your doctor for specific instructions about stopping these and other drugs before testing.
Skin tends to be over-reactive to testing in people with dermatographism (see p. 52). Blood tests for specific IgE,
such as RASTs (see p. 92), are needed for anyone who has this condition. Eczema sufferers with a rash over large areas of the body may also require blood tests, if there is too

little clear skin for testing.
Skin-prick tests can produce both false positives and false negatives (see box below). Some allergic diseases will give a lot of false negatives and relatively few false

positives, while for others the reverse is true. The allergen itself influences the rates of misleading reactions: for example, tests for soya allergy are notoriously

unreliable, whereas those for peanut are far more accurate. The age of the person being tested also makes a difference. With all these influences at work, interpreting the test

responses is a real art, and the doctor’s experience counts for a lot.
All sorts of people offer skin-prick tests, including alternative practitioners. Get them done by a qualified doctor, preferably by an allergist, who will know how to make sense

of the reactions.
Note that the purpose of these tests, and of blood tests for specific IgE, is to identify the allergens that are bringing on your symptoms, not to predict how strongly you will

react to those allergens. The tests may give some Indication of the intensity of your reaction, but they cannot be regarded as a good guide to how you will respond to the

allergen in the future.
The safety record of skin-prick tests is very good. Occasionally a systemic reaction (anaphylaxis) occurs with these tests, but there are no records of any deaths. Nevertheless,

if you suffer from severe asthma or have experienced anaphylactic shock in the past, it is advisable for the doctor to have adrenaline and resuscitation equipment available.

Those with strong allergic reactions to latex may also react badly if they are tested with an allergen that cross-reacts with latex (e.g. cypress pollen), not just when tested

with latex itself. Taking beta-Mockers (see box on p. 150) increases the risk of a life-threatening reaction for anyone in these higher-risk categories.
False positives and false negatives
Apart from challenge tests, none of the tests used for allergy works with 100% accuracy. Most give both false positives and false negatives.
A false positive means that there is a positive test but no actual reaction when the allergen is encountered (e.g. eaten or inhaled). A false negative means that there is a

negative test result despite a genuine reaction (as shown by a challenge test, for example).
A test that gives relatively few false positives has good positive predictive value – in other words, if it suggests you are allergic to something, you probably are.
A test that gives relatively few false negatives has good negative predictive value. If it comes up negative, you are probably not allergic to that allergen.
Some tests for allergic reactions show good positive predictive value but poor negative predictive value, while for other tests the reverse is true.

Skin-prick tests
This is an indirect method of detecting true allergic reactions. It is one of a family of skin tests that use a similar approach. The three different tests in this family are known as: skin-prick tests or prick tests, puncture tests, and scratch tests.
For the skin-prick test - the technique used in Britain - a small drop of liquid containing an allergen, such as grass pollen, is placed on the arm. The doctor makes a small prick in the skin, under the drop of liquid, allowing a minuscule amount of the allergen to get into the skin. A positive reaction is recorded if a red bump develops soon afterwards. For accuracy, the bump must be compared to positive and negative controls (see below).
The puncture method is very similar to the skin-prick test but uses a slightly different technique for breaking the skin. The term prick-puncture test covers both techniques.
With the scratch method, the skin is scratched lightly, and the allergen solution is then applied over the scratch. This method gives less consistent results than prick-puncture testing.
It is important to include a negative control in the test - a skin-prick test with plain salt water (saline). This should not produce much of a bump - if it does, the skin is clearly over-reactive and the tests more difficult to assess. The doctor should also include a positive control - a skin-prick test with histamine, the substance that plays a central role in allergic reactions. This should always produce a bump. If it does not, the skin is decidedly under-reactive, and the tests are invalid.
Taking antihistamines will make the skin under-reactive, and you should stop taking them before the testing, for a period ranging from a day to several weeks - it varies depending on the particular antihistamine. Ask your doctor for specific instructions about stopping these and other drugs before testing.
Skin tends to be over-reactive to testing in people with dermatographism (see p. 52). Blood tests for specific IgE,
such as RASTs (see p. 92), are needed for anyone who has this condition. Eczema sufferers with a rash over large areas of the body may also require blood tests, if there is too little clear skin for testing.
Skin-prick tests can produce both false positives and false negatives (see box below). Some allergic diseases will give a lot of false negatives and relatively few false positives, while for others the reverse is true. The allergen itself influences the rates of misleading reactions: for example, tests for soya allergy are notoriously unreliable, whereas those for peanut are far more accurate. The age of the person being tested also makes a difference. With all these influences at work, interpreting the test responses is a real art, and the doctor’s experience counts for a lot.
All sorts of people offer skin-prick tests, including alternative practitioners. Get them done by a qualified doctor, preferably by an allergist, who will know how to make sense of the reactions.
Note that the purpose of these tests, and of blood tests for specific IgE, is to identify the allergens that are bringing on your symptoms, not to predict how strongly you will react to those allergens. The tests may give some indication of the intensity of your reaction, but they cannot be regarded as a good guide to how you will respond to the allergen in the future.
The safety record of skin-prick tests is very good. Occasionally a systemic reaction (anaphylaxis) occurs with these tests, but there are no records of any deaths. Nevertheless, if you suffer from severe asthma or have experienced anaphylactic shock in the past, it is advisable for the doctor to have adrenaline and resuscitation equipment available. Those with strong allergic reactions to latex may also react badly if they are tested with an allergen that cross-reacts with latex (e.g. cypress pollen), not just when tested with latex itself. Taking beta-Mockers (see box on p. 150) increases the risk of a life-threatening reaction for anyone in these higher-risk categories.
False positives and false negatives
Apart from challenge tests, none of the tests used for allergy works with 100% accuracy. Most give both false positives and false negatives.
A false positive means that there is a positive test but no actual reaction when the allergen is encountered (e.g. eaten or inhaled). A false negative means that there is a negative test result despite a genuine reaction (as shown by a challenge test, for example).
A test that gives relatively few false positives has good positive predictive value - in other words, if it suggests you are allergic to something, you probably are.
A test that gives relatively few false negatives has good negative predictive value. If it comes up negative, you are probably not allergic to that allergen.
Some tests for allergic reactions show good positive predictive value but poor negative predictive value, while for other tests the reverse is true.
Fresh is best
The fruit and vegetable allergens that provoke Oral Allergy Syndrome (see p. 63) are chemically unstable, so commercially produced extracts for skin-prick testing quickly lose their potency and give false-negative results. Most allergists now favour using a drop of fresh juice from the fruit or vegetable concerned.
Intradermal tests
These tests (also called ‘intracutaneous tests’) put allergen more deeply into the skin than prick-puncture tests. The skin tends to react more when penetrated to this depth, so there are more false positives. There is also a greater risk of a serious reaction which may require emergency resuscitation. Don’t undergo these tests if you are taking beta-Mockers (see box on p. 150).
Blood tests for IgE
There are blood tests that look at the total amount of IgE (the allergy antibody), which is sometimes useful in diagnosis. But more important are blood tests for specific IgE – against egg or grass pollen or latex, for example. There are different ways of measuring the IgE in the blood, the most commonly used being a radio-allergosorbent test or RAST.
Research shows that RASTs are no more accurate than skin-prick tests in confirming real-life allergic reactions. However, they are useful for patients who can’t discontinue their antihistamines without developing severe symptoms, and for those with dermatographism or very severe eczema (see p. 91).
Patch tests
These tests, used primarily for contact dermatitis, are similar to straightforward challenge tests, because the suspect substances are applied directly to the skin.
The test substances are placed on the skin – usually on your back – in small chambers. They are held in place with sticky tape, and left there for several days. Ideally, the reaction of the skin should be checked three times: after two days, again the next day, and again the day after that. It really is worth going back for all these separate visits, because the accuracy of the test increases greatly with repeated checking.
The substances chosen for testing are a standard set of antigens that most commonly cause contact dermatitis. This standard set will pick up 60-80% of all sensitivity reactions in contact dermatitis. If you have substances that you suspect may be causing symptoms, such as cosmetics, the doctor can usually test for these too.
You should not be tested while you still have a rash, as the testing will probably make the existing rash flare up, even though the test patches are applied well away from the rash.
Use of steroid creams and any light treatments (including exposure of the test area to ordinary sunlight) must stop at least a week before testing starts, or the results will not be accurate.
Interpreting patch tests requires a huge amount of skill, plus extensive knowledge of the finicky details of the different test substances. You need a dermatologist with considerable experience in this area.
False positives (see box on p. 91) can occur, especially if you react very strongly to one of the substances tested – some people develop what dermatologists call an ‘angry back’, and this generates false positives to various other substances being tested at the same time. Should you be told that you are sensitive to a great many different things, you may want to query this reading of the test. Ernest N. Charlesworth, an allergist and dermatologist at the University of Texas, describes patients who ‘develop into environmental cripples’ after being told that they are definitely sensitive to multiple antigens, on the basis of misinterpreted false-positive patch tests.
False negatives (see box on p. 91) are also possible, even with very careful testing. Should this occur, a type of challenge test known as a ROAT (Repeat Open Application Test) is possible. The suspect substance is applied to the inner fold of the elbow twice a day for a week. Get your doctor’s agreement before trying this test.
Endoscopy and biopsy
Miniaturised cameras and sophisticated fibre-optics have allowed modern doctors to do something that their predecessors could never have imagined possible – look right inside the human body. This procedure is called endoscopy, and it has a useful role in a few sensitivity reactions.
Looking inside the sinus cavities can assist in understanding exactly what is going wrong in chronic sinusitis. Inspecting the digestive tract can be valuable in several of the non-IgE immune reactions to food, such as coeliac disease (see p. 70) and eosinophilic gastroenteritis (see p. 72).
A biopsy is often carried out at the same time as endoscopy.
s involves taking a small sample from the affected area, such as
I ning of the gut, and studying it in detail under a microscope.
One purpose of a gut biopsy is to look for characteristic :goes of damage to the lining of the gut – such as the distinctive charges produced by untreated coeliac disease. A biopsy can also reveal what kind of immune cells are present. Abnormal numbers of certain immune cells, for example, eosinophils (see p 19), may suggest a particular diagnosis.
Another way of looking at what kind of immune reactions are going on, used for lung diseases, is a bronchoalveolar lavage – iterally a ‘washing out’ of the airways and lungs, allowing immune cells to be collected and studied. This diagnostic technique is lased for Heiner’s Syndrome (see p. 72).
Tests for food intolerance
The only really effective way of testing for food intolerance is an el ruination diet (see pp. 194-7). This is the gold standard. However, it is neither easy nor quick – which has led to a constant search for alternative tests.
The proposed alternatives are all indirect tests, that is to say, non-dietary. The results of the tests are used as a basis for an avoidance diet. In other words, the foods that give a positive test result are avoided.
Some of these tests use samples of hair or blood, others use pulse testing, pendulums, or muscle strength tests (’applied kinesiology’). A few of these tests do show some promise. Pulse tests, and a blood test called the ‘lymphocyte transformation test’. for example, can give a general indication of sensitivity reactions – sometimes. However, even in the most expert hands, these do not give a result that is accurate enough to be useful.
Of the other tests that are available, most have not been evaluated at all objectively.
Many of them are advertised directly to the public, and one of the problems with this approach is that the testing company starts by assuming that food is the problem. The same is usually true of ‘dietary therapists’ and others in the alternative health field offering tests of this kind.
Almost everyone who undertakes such tests is given a fairly long list of foods which have come up positive in the tests. This does not fit with the evidence from medical trials in which a group of people with irritable bowel or migraine (typical food intolerance symptoms) undertake an elimination diet. A significant proportion of them always find that they do not have food intolerance. Of the rest. many find that they react to one or two foods only. The long lists of foods produced by the commercial tests are, to put it mildly, implausible.
With tests that require a sample of blood, sending off two blood samples from the same person, under different names, is a simple way of assessing the tests’ validity. This exercise has been tried several times with different testing companies, and every time two completely different lists of foods have been sent back.
Covert studies of this kind have also shown that the tests overlook genuine reactions. In one alarming case, a woman with a true allergy to peanuts was assured by a ‘dietary therapist’ that she really could eat peanuts safely.
Many people with food intolerance will tell you that they did well after following a diet based on such tests – and they may well have done. Given that common foods such as wheat and milk are regular offenders in food intolerance, and that these foods very frequently feature on the lists of positive test results generated by commercial testing companies, quite a few people should do well. The problem is that these people may also be avoiding many other foods quite unnecessarily.
Furthermore, if people have sensitivities to some other foods that are not on the list, they will be missing out. They could enjoy a far better level of health if all the foods causing symptoms were Identified and removed from their diet.
In the end, an elimination diet is both cheaper and far more likely to give the right answers.
Testing for IgG antibodies
In diagnosing food intolerance, a few doctors offer tests for a type of antibody called IgG. This antibody is formed to any food molecules that get Into the bloodstream after a meal – and some do, even in entirely healthy people. So finding IgG antibodies to food molecules is not indicative of any disease at all. It occurs in everyone and is perfectly normal.
Nevertheless, some doctors feel that by measuring the level of IgG antibodies to foods, they can get a general idea of the permeability of the gut wall (which might possibly be true) and of particular foods that could be causing intolerance reactions (very doubtful – the tests just tell you what you eat most, and you know that already).
This test does measure something real, unlike some of the alternative tests for food intolerance. But the relevance of what it measures to the health of the individual concerned is partial and indefinite. A recent study of IgG testing for irritable bowel syndrome has confirmed this view.
In short, blood tests for IgG antibodies to food molecules seem like very poor value for money, and potentially misleading, whereas an elimination diet is a far more precise way of pinpointing food intolerances.

Allergy and Your Immune System
`The summer used to be such a miserable time for me because I’m allergic to grass pollen. For most of

my life I have had dreadful hayfever, and my asthma would get worse during the summer as well.

Antihistamines knocked me for six, and although there were nose drops that helped a little, they

certainly did not resolve the problem completely. Exam time was always a nightmare when I was a student

- then, as now, it coincided exactly with the pollen season.’
‘Getting a job in Chicago was a turning point in my health. My colleagues were amazed to see me

snuffling through the summer and just accepting that nothing could be done to improve matters. The

whole approach to treating allergies is different there. Eventually someone marched me off to see her

allergist, who said that I should have “allergy shots” and that my health insurance would cover it. The

process was very time-consuming at first, and it took a while to work, but the change is remarkable.

I’ve never regretted having the treatment. Summer is a time I can actually enjoy now.’
Not everyone responds this well to immunotherapy, but for those allergy sufferers who do benefit, this

is an excellent treatment. It tackles allergies right at their source, by teaching the immune system to

react differently to the allergen.
Also known as Specific Immunotherapy (SIT), Incremental Immunotherapy (11T) or simply as

hyposensitisation, this form of treatment was devised by two English medical researchers, Leonard Noon

and John Freeman, who reported their successes with hayfever patients in 1911. Ironically, their

treatment is now less readily available in Britain than in any other industrialised nation. Only a

small minority of British allergy patients receive immunotherapy. The cause of this strange situation

is a ruling made in 1986 by the Committee on the Safety of Medicines (CSM). This states that

immunotherapy must only be given where there is resuscitation equipment available, and that all

patients must wait for an hour after each injection, in case of
side effects. In addition, immunotherapy cannot be used for severe asthma.
The requirement for resuscitation equipment rules out most GP surgeries, and this effectively puts

immunotherapy beyond the reach of many allergic individuals in Britain, owing to the extreme shortage

of allergists and hospital allergy clinics (see p. 89). (In the past, the lack of allergy specialists

meant that most immunotherapy in Britain was given by GPs.)
The CSM ruling was triggered by a number of deaths due to immunotherapy: there were eleven fatalities

between 1980 and 1986, with five of these in the eighteen months just before the report. But almost all

these deaths were due to very basic errors in the way the injections were given – tragic as the deaths

were, the official response to them was inappropriate. Fatal reactions to immunotherapy can be avoided

with close attention to ordinary safeguards (see p. 166-7).
Allergen immunotherapy is still freely available elsewhere in the world, and is regarded as a key part

of allergy treatment. Britain is now out of step with all other developed countries, and most doctors

feel that British restrictions are far too strict.
There are hopes that this situation may change within the next few years, and that more allergy

sufferers may be able to take advantage of this valuable treatment. This could be achieved, in part, by

investing more National Health Service money in allergy clinics and allergy specialists. In addition,

there should be a relaxation of the regulations, so that properly trained GPs can give immunotherapy to

patients who are not at high risk of a fatal reaction. For people whose lives are affected by

allergies, the reintroduction of this treatment (with appropriate safeguards) would be a huge boon.
The uses of immunotherapy
Immunotherapy is mainly used for airborne allergens such as pollen, house-dust mite and mould spores.

Allergies to animals can also be treated with immunotherapy, but the treatment cannot work miracles –

if a cat-allergic person decides to keep the cat, the high dose of allergen inhaled every day limits

the impact of immunotherapy treatment.
People with straightforward allergic reactions affecting the nose and eyes (allergic rhinitis and

conjunctivitis) respond well to immunotherapy. In patients with hayfever, for example, the success rate

(patients showing some degree of improvement) is about 80-90%. When nasal allergies are complicated by

chronic sinusitis or nasal polyps, the chance of success is a little lower.
Some studies of the long-term effects of immunotherapy suggest that, if it is given to children with

hayfever or perennial rhinitis, those children are less likely to develop asthma.
The benefits of using immunotherapy to treat established asthma are less certain. Asthma is a more

complex disease than hayfever, and allergies are only one factor among many (see p. 36), which may

limit the impact that immunotherapy can make. Experience suggests that immunotherapy can be a great

help for an asthmatic with a strong allergic reaction to a single airborne allergen, such as grass

pollen or house-dust mite, but not for other asthmatics. Asthmatics with aspirin sensitivity or chronic

sinusitis are unlikely to benefit.
The value of immunotherapy to children with asthma is a subject of great debate among doctors in the

United States. Some studies suggest that it is of little real benefit, while others are more positive.

One interesting study, that followed asthmatic children for 15 years or more, found that if they were

given a full five-year course of immunotherapy when young, they tended to have fewer asthma symptoms

and need less medication in their late teens and early twenties.
Chronic urticaria (nettle rash) is occasionally due to airborne allergens, in which case immunotherapy

may help. However, immunotherapy is not recommended for atopic eczema. When people with both eczema and

rhinitis try immunotherapy for their nasal allergies, some find that their eczema gets worse.
Insect-sting allergy is a prime candidate for immunotherapy (see pp. 167-8) but food allergy is a

different matter, and is not treated with immunotherapy at present (see p. 168).
Who can get immunotherapy?
As a result of the CSM ruling (see p. 164) remarkably few allergy sufferers in Britain receive

immunotherapy.
Those with insect-sting allergy, who have suffered anaphylaxis (see p. 58), are the most likely to be

offered this treatment. However, even with this frightening and life-threatening problem, which can be

treated with almost 100% success by immunotherapy (see p. 167-8), such treatment is not automatically

available.
A few people with severe hayfever that does not respond well to drug treatment may also be given

immunotherapy. It is worth asking your doctor about such treatment if you feel you would benefit.
How immunotherapy works
Immunotherapy consists of a series of small injections, just under the skin. The liquid that is

injected contains an extract of the offending allergen, for example house-dust mite. The injections are

given at regular intervals, usually once a week, although other schedules are possible (see p. 167-8).
At the outset, a very dilute version of the allergen extract is used, way below the threshold for an

allergic reaction. People who seem highly sensitive, on the basis of their skin tests, start on an

extract that is even more dilute.
For the next injection, a slightly higher concentration of the allergen extract is used, and the

concentration goes on increasing with each successive injection. The idea is to habituate the immune

system to the offending allergen, by very gradually raising the dose. Eventually, when the dose reaches

a level which generally gives beneficial effects, no further increases are made.
If an allergy sufferer reacts badly to immunotherapy injections (see p. 166) on several successive

occasions, the dose may be levelled off before the ideal maximum dose is reached. However, a good

allergist will persist for some time in trying to increase the dose because stopping at a lower level

often results in the treatment being ineffective.
The first stage of immunotherapy, when the concentration of allergen is being increased week by week,

is referred to as the build-up stage. The second stage, when the dose is being kept at the same level,

is called maintenance therapy, and the dose used is the maintenance dose.
There is sometimes an obvious improvement by the time the build-up stage is complete, but not always.

The benefits of the treatment generally appear within six months of reaching the maintenance dose, but

some people have to wait a year or even two before things improve. As the immunotherapy begins to take

effect, symptoms decline and there is often less need for drugs.
A great deal of research effort has gone into finding out what lies behind these changes – in other

words, what is actually happening to the immune system when immunotherapy is effective. The answer is

that a surprising number of different changes may occur and no two allergy sufferers react to

immunotherapy in quite the same way. Frequently there is a shift in the kinds of antibodies the body

produces against the offending allergen. Levels of IgG antibodies (which help to block the allergic

reaction) go up, while levels of the allergy antibody, IgE, tend to stabilise and eventually go down.

The numbers of mast cells (see box on p. 12) may also decline, and they can become less responsive to

the allergen. The balance of power between Th1 cells and Th2 cells may also shift, with the pro-allergy

Th2 cells (see p. 11) becoming less influential.
What can go wrong
The secret of safe immunotherapy is to go at exactly the right speed for the immune system of the

individual being treated. The doctor should look for feedback from the immune system – signs that show

how well it is coping with the steadily increasing dose of allergen – and use these to pace the

immunotherapy schedule.
Going too fast – getting ahead of the immune system’s ability to cope – is hazardous. A major allergic

reaction, called anaphylaxis (see p. 58), can occur, and this is the cause of deaths during

immunotherapy. However, as long as there is injectable adrenaline (see p. 150) and resuscitation

equipment available, even such an extreme crisis can be dealt with safely.
Serious reactions to immunotherapy usually occur:
•    during the initial build-up phase; maintenance therapy is much safer
•    during the pollen season, for those with pollen allergy
•    when a new vial of allergen extract is first being used, because of variations in concentration

(see p. 168-9).
Those most vulnerable to severe reactions are:
•    people with asthma, especially severe or unstable asthma
•    those who have experienced systemic allergic reactions in the past
•    anyone who appears to be extremely allergic, on the basis of skin tests
•    anyone taking beta-Mockers (see box on p. 150).
With care, these fatalities can be avoided. Patients who are given immunotherapy can ensure their own

safety by being well informed about the procedure (see p. 167).
The timing of immunotherapy
There are various different approaches to the timing of immurotherapy. The basic method (which has a

good safety record in the United States where it is very commonly used) starts with injections once a

week. After the maintenance dose has been reached, maintenance injections are given once every 2-4

weeks. The frequency of these may be increased during the pollen season, for people with pollen

allergies.
It is the regularity of the injection schedule that gradually creates, and then sustains, immune

tolerance, so the treatment is only of value to patients who can reliably keep their appointments.
When immunotherapy is successful, it can eventually be discontinued without any reappearance of the

allergic reaction. It usually takes 4-5 years of regular therapy, from the time of the first injection,

to get to this point. The benefits then persist for many years, perhaps indefinitely in some people,

even without any further injections.
Rush immunotherapy
Trying to speed up the process of immunotherapy greatly increases the risk of a severe reaction

(anaphylaxis). However, there are some situations where fast results are needed, and in such cases rush

immunotherapy, also called accelerated immunotherapy, may be used.
During the build-up stage of rush immunotherapy, injections are given every day, or even several times

a day. All the usual safety procedures (see below) are observed with particular care, to reduce the

chance of a severe reaction.
In semi-rush immunotherapy, the build-up injections are given twice a week, and the risks are lower

than with daily injections, but still higher than with weekly injections.
Minimising the risks
If you are lucky enough to be offered immunotherapy treatment under the National Health Service, you

should not feel concerned about accepting the offer. There is very little risk of a bad reaction

because safety procedures are now so stringent.
To minimise the risk of suffering a severe reaction, the doctor will ask you, at each visit, about any

reactions that occurred after your previous injection. Reactions might include redness, itching or

swelling around the injection site, or (more seriously) symptoms elsewhere on the body, such as nettle

rash (urticaria), itchy skin, sneezing, a runny nose, red or itchy eyes, tightness in the throat or

chest, coughing or wheezing. Always make a note of such symptoms, so that you don’t forget to mention

them at the next visit. This is crucially important, as such reactions can indicate that the immune

system is being hurried along too fast.
The doctor will also ask if you have an infection of any kind, as this can alter your reaction. You

should also tell the doctor about any new medicines being taken, as some, such as betablockers (see box

on p. 150), can make a bad reaction to the injection more likely to occur.
Asthmatics can expect the doctor to ask about current asthma symptoms, and to check their peak flow

both before and after an injection. If there are any symptoms, or if the peak flow is less than 70% of

the best-ever value, the injection won’t be given.
Severe reactions can sometimes begin several hours after the injection, so stay within reach of a phone

for about 24 hours. Among United States allergists (who don’t require their patients to wait after the

injection for more than 20-30 minutes) there are some who believe that everyone undergoing

immunotherapy should carry an adrenaline (epinephrine) auto-injector (see p. 150) on the day an

injection has been given, for use in the event of a severe reaction. Anyone who has suffered

anaphylaxis in response to an insect sting will probably have an adrenaline auto-injector anyway, and

this can certainly be used to treat anaphylaxis following immunotherapy. Note, however, that using the

adrenaline is just the first step in treating anaphylaxis (see p. 98) and you must then go back to your

allergist, or to the nearest hospital emergency department, without any delay.
It is sensible to avoid exercise for two hours after an injection. Be extra-cautious during the pollen

season if you are receiving immunotherapy for pollen allergies.
Immunotherapy for insect-sting allergy
`Our daughter has had two really bad reactions from being stung by a wasp. After the second one, the

doctor at the accident and emergency department told us that she nearly died. We got so anxious about

it that we worried every time we left the house in the summer, and it was even worse if she went out

without us. My wife got so upset about it that she wasn’t sleeping well. It was affecting the whole

family badly.
‘Then we heard about desensitisation treatment, and asked our GP, but he said he couldn’t do it.

According to him, they might be able to do it at the hospital, but it might not work, and it was risky

too. We accepted that at first, but then I started doing some research on the Internet, and discovered

that in America and Germany this treatment is absolutely standard – someone like our daughter would

automatically be given it. We felt very angry when we found this out, and went back to the doctor.

Eventually Ann was referred to the allergy department at a hospital, and now she is getting this

desensitisation treatment. I’m pleased about that, obviously, but I still think it shouldn’t have been

such a fight to get it.’
Immunotherapy provides highly effective protection for those with insect-sting allergy, and should be

given to anyone who has had a severe systemic reaction (see p. 60). Some United States allergists also

recommend it for adults who have had a cutaneous systemic reaction (see p. 60), on the basis that they

may well progress to a severe systemic reaction with the next sting.
Studies of people who have suffered severe systemic reactions, and are then treated with immunotherapy,

show that 97% have no systemic reaction to future insect stings. For the 3% who are not fully

protected, the severity of the reaction is much reduced and far less likely to be life-threatening. In

other words, this is an excellent treatment which can save lives.
Targeting the treatment
Choosing the right venom for immunotherapy can sometimes be difficult. Not everyone with insect-sting

allergy sees the insect that caused the reaction. Skin tests may not give the answer either, because

there are often positive reactions to several different venoms. Some of these may be false positives

(see box on p. 91) and it is impossible for the allergist to say which one(s) are actually relevant.

Most allergists will recommend immunotherapy for all of them, using a mixture of venom extracts.
Where the guilty insect was seen and identified, but other venoms also give positive skin tests, a more

difficult decision has to be made. Many allergists carry out immunotherapy for all the venoms that gave

a positive skin test, on a ‘better safe than sorry’ basis. Since there are cross-reactions between

venoms (see box on p. 113), there is some sense in this. Other allergists just give immunotherapy for

the insect that did the deed.
Will immunotherapy against one insect protect against a related insect? With two closely related

insects such as wasps and hornets, which have many allergens in common, it might do – but there is no

guarantee. The problem is that, as well as the shared allergens, each venom also has its own unique

ingredients. It’s impossible to say, with the kind of tests available at present, if an allergic

reaction was to shared allergens or unique ones. So immunotherapy against wasp venom may give

protection against hornet venom, but it will not necessarily do so – and vice versa.
In the case of bumblebee allergy (seen almost exclusively in those, such as horticulturalists, whose

work involves handling bumblebees) a more definite answer can be given – honeybee immunotherapy does

not work. Immunotherapy with bumblebee venom does work, fortunately. The bumblebee extract has to be

obtained from specialist sources.
Injections are given weekly during the build-up phase, unless protection is needed urgently, as with

work-related sting allergy, in which case rush immunotherapy may be used. Once the maximum dose has

been reached, a maintenance injection is needed every four weeks. After a year, this maintenance dose

can be given every 6-8 weeks.
After 3-5 years of immunotherapy, skin tests with insect venoms are usually tried again. If the results

are negative, the immunotherapy will stop. Research now shows that, even if skin tests are still

positive when immunotherapy ends, there’s an 8090% chance that no systemic reaction will occur to

future stings. Some people are not reassured by this, and prefer to continue with immunotherapy for

their own peace of mind. Indeed, research shows that a near-fatal systemic reaction has a long-lasting

psychological impact, and that many people continue to feel anxious despite completing immunotherapy

and reacting negatively to skin tests.
At one time, challenge stings with live insects were given to check whether immunotherapy had actually

worked. Few doctors do this now, but your allergist may be prepared to do a challenge test if you ask.

Adrenaline and resuscitation equipment would be available if a challenge test were used, so any severe

reaction could be dealt with promptly and effectively. The fact that the psychological consequences of

insect-sting allergy are so persistent suggests that challenge tests with live insects may have a

particular value, in demonstrating that immunotherapy has worked. Challenge tests are also helpful for

those who work with stinging insects, such as honeybees and bumblebees, and who need to be sure that

they can go back to work safely.
Immunotherapy for food allergy?
Attempts to use standard immunotherapy for food allergy have been made repeatedly, but without success.

The process of giving the injections is nerve-racking because of the constant risk of a severe

reaction. The risks prevent the dose of allergen being increased very much, so the beneficial effects

are small. While there may be some reduction insensitivity, it is not enough – or not reliable enough –

to be of any practical value.
What doctors are aiming for here, incidentally, is simply to protect against the effects of

accidentally eating a tiny amount of the food – no one is expecting that someone with peanut allergy

will be able to eat peanut butter sandwiches as a result.
Some of the new developments in immunotherapy may be useful for food allergy, as described in the next

section.
The future of immunotherapy
Many different research teams are working on ways of improving immunotherapy – making it more

effective, safer to give, and less time-consuming.
One approach involves altering the allergen, so that it only interacts with those parts of the immune

system whose job is to control allergic reactions (and therefore bring about tolerance). The changes

made to the allergen are designed to make it ‘invisible’ to the parts of the immune system that

actually attack the allergen. The idea is to inject something that can’t cause a bad reaction, and is

therefore 100% safe.
The modified allergens are called allergoids. Another term often used is peptide immunotherapy – this

describes a technique in which the allergens are chopped up into small pieces to make them safe

(allergens are proteins, and a fragment of a protein is called a peptide).
Already, researchers in Germany have made an allergoid from birch pollen that can reduce hayfever

symptoms with a series of just seven injections given before the pollen season.
Meanwhile, a research team in London is working on peptides made from cat allergen, with encouraging

results so far. In a group of asthmatics who were allergic to cats, a series of 4-10 injections, over a

period of 2-8 weeks, produced benefits in about half those treated. The researchers believe that they

can improve on this and help the majority of people with cat allergy, at least enough to survive

temporary exposure to cat allergen (when visiting cat-owning friends, for example). They hope to refine

the treatment sufficiently to enable some cat-allergic people to keep their pet, rather than finding it

a new home. This is a relatively safe treatment that might be given by a GP, rather than only by

specialists. The research team hopes the treatment will be available by about 2009.
Could this kind of technique work for food allergy? Doctors believe that it can, and a great deal of

research work is being done, in both Britain and the United States. A major focus of this effort is

peanut allergy, since this puts so many young lives at risk. Even if the research is successful, It

will be several years before such treatments become available.
Researchers are also working hard to produce standardised allergen extracts – in other words, allergen

extracts that always contain a standard amount of the allergen. The aim is not only to reduce the

number of treatment failures (which can occur if the extract does not contain enough allergen) but also

to avoid mishaps when a new vial of allergen extract is used (differences in strength, between one vial

and another, are sometimes a cause of anaphylactic reactions).
Standardisation is difficult, because the starting materials –skin particles from horses, for example,

or dust-mite droppings –are natural materials and therefore variable. Some samples contain far more of

a particular allergenic ingredient than others.
One way around this problem is to develop accurate methods of measuring the amount of allergen in the

extract. Another approach is to abandon the whole business of making extracts, and produce allergens

artificially, in a laboratory. This is done by inserting the gene for the allergen – the gene for the

Der p1 allergen of house-dust mite, for example – into bacteria. These bacteria then act as production

units, manufacturing large amounts of the allergen every day. With this high-tech approach, the exact

content of the allergen preparations can be controlled.
These high-tech allergen preparations are extremely pure, and therefore very effective – as long as the

person receiving immunotherapy really is sensitised to the particular allergen that is included.

Unfortunately, most natural allergenic materials contain two, three or even more separate allergens. In

house-dust mite droppings, for example, while Der p1 is the allergen that affects most people, there is

also an allergen called Der p2, and a few people are more sensitive to this than to Der pl.
Artificially produced allergen preparations usually include the main allergen only. For the minority of

people who are more severely allergic to one of the other allergens, this extract will not work.

Eventually this problem will no doubt be circumvented by means of more precise skin testing before

immunotherapy begins – skin tests with individual allergens, rather than with allergen extract

containing a mix of allergens.
A third approach is to change from injections to oral immunotherapy – giving the allergen extracts by

mouth. The best results are obtained when the allergen is held under the tongue for a while and then

swallowed. This is known as Sub-lingual immunotherapy or SLIT, and has become very popular in Italy and

France, where it is a common treatment for hayfever. A recent pilot trial among GPs in Britain suggests

that it may be useful, but is not a miracle cure. Overall, the group treated with SLIT had fewer

symptoms during the pollen season, but antihistamines were still needed. There is some evidence from

Italy that SLIT might reduce the likelihood of children with hayfever going on to develop asthma, and

reduce the chance of new sensitivities.
Side effects are unusual with this treatment, and those that do occur are mostly mild – itching in the

mouth, for example. The treatment is safe enough for routine use in children.
Might oral immunotherapy work for food allergy? Other Italian studies suggest that it could. The

objective of these studies is to reduce the risk to children with cow’s-milk allergy from accidental

encounters with ‘hidden milk’ in prepared food or drink. The immunotherapy treatment begins with

miniscule amounts of milk – the doctors start with a single drop diluted in water, each day for a week

– and increase the dose extremely slowly. Antihistamines are given to minimise the risk of a reaction.
The whole process requires enormous patience, but after seven months, the majority of the children

involved can tolerate some milk – between three tablespoonfuls and a small cupful each day.
This is a very encouraging study that should be repeated by doctors in Britain. Because of the risks of

anaphylaxis – which can, of course, be fatal – it does require full medical supervision, and you should

not attempt it at home. Whether this method would work for allergens other than milk is something that

nobody has yet investigated.
A great many other approaches to immunotherapy are currently being tried for food allergy. Many of the

new techniques are highly experimental, and some show great promise, but it will be many years before

they are in use.
One innovation that is closer to being in general use in the United States involves giving the anti-IgE

drug omalizumab (see p. 149) alongside immunotherapy injections. The drug maximises the benefits from

the immunotherapy, and may make the build-up stage (see p. 165) safer, by lowering the risk of

anaphylaxis. For British allergy sufferers, who cannot yet get omalizumab, and whose chances of getting

immunotherapy are vanishingly small, it may seem unkind even to mention such treatments, but we can

only hope that things will improve here in the near future. You might take some comfort from the

thought that, by the time immunotherapy is available again in Britain, there will be a whole host of

highly effective new techniques available for doctors to try.
All the methods described above are forms of specific immunotherapy – they treat an allergy to dust

mites or to grass pollen or some other specific allergen.
A far more radical and ambitious approach to immunotherapy is now the aim of some medical researchers:

blocking the tendency to allergies as a whole.The underlying idea here is to reverse the basic shift in

the immune response, from Th1 cells to Th2 cells. It is this shift to Th2 cells which produces the

allergic tendency (see pp. 11 –13).
Some interesting findings have already been made in this area, including the surprising discovery that

the balance of Th1 cells and Th2 cells can be adjusted even in people with longstanding allergies.

Inspired by discoveries about hygiene and allergy (see p. 21), British researchers have made a vaccine

containing inactivated cells of a harmless bacterium found in the soil, Mycobacterium vaccae. This is

given as a single injection just under the surface of the skin. It has been used for adult patients

with asthma, and for children with severe atopic eczema, with some improvement in both groups. If the

treatment proves as useful as the preliminary studies suggest, this could be a common treatment in a

few years’ time.