Posts Tagged ‘chronic urticaria’

When Leonard Noon reported his first tentative experiments with immunotherapy for hayfever, in 1911 (see p. 164), he believed that pollen contained a toxin. Most people were

‘immune’ to this toxin, he said, in the same way that people might be immune to measles or diphtheria, but hayfever sufferers lacked this immunity. Noon thought that his

steadily increasing doses of pollen, injected just under the skin, were inducing immunity to the pollen toxin, in the same way that a smallpox vaccine could induce immunity to

smallpox.
Noon’s theory was all wrong, as we now know, but the important thing was that the treatment seemed to work. In fact it transformed the lives of some patients, especially those

who were very severely affected by hayfever. One spoke of a ‘marvellous cure’, another of going for walks to kick my old enemy the hay’.
So doctors kept using Noon’s treatment, and in time — when it became clear that Noon’s theory was flawed — medical researchers began trying to figure out how the injections

really worked.
Surprisingly, they have still not succeeded, even though a great deal is now known about the changes that can occur in people undergoing immunotherapy. Despite a wealth of

detailed knowledge (see p. 166), it remains impossible to say exactly how conventional immunotherapy reduces allergic reactions. Surprising discoveries about the effects of

conventional immunotherapy are being made all the time.
New methods of immunotherapy are still being devised today, and there are three different approaches being taken.
Firstly, there are doctors experimenting with modifications of the technique devised by Noon. For example, instead of injecting the allergen extract, some doctors are giving it

to their patients in capsule form. to be swallowed. Others are giving it as a liquid, to be placed under the tongue and held there for a few minutes, then swallowed (see p.

169). Sound scientific trials show that both these methods work well, at least with some allergens.
There are also experiments with speeded-up immunotherapy
(see p. 166), called ultrarush techniques — at the outset, injections are given at hourly intervals, or even more frequently (in hospital, of course, where severe reactions can

be dealt with immediately). Doctors have found that they can induce a remarkably rapid tolerance of the allergen in this way.
The second approach is to apply modern medical knowledge about allergic reactions and so develop entirely new methods of immunotherapy (see p. 168-9). Such research involves

working out, from first principles, novel ways of modifying the immune response in general, or the reaction to one allergen in particular.
This theory-led approach is certainly successful for classical allergies such as hayfever and perennial allergic rhinitis, where there is a good understanding of the basic

mechanism (i.e. the malfunctions of the immune system that produce the disease). But for those diseases where the underlying mechanism is only partially understood, such as

atopic eczema, this approach is not necessarily the best one. And for diseases such as food intolerance, where the cause of the illness remains largely unknown, it is a complete

non-starter.
The third type of approach is to devise a technique by trial and error, and then puzzle out the ‘how’ question later. This is the same sort of path as Noon originally took, and

some believe that this kind of pragmatic experimental approach — practising a method which seems to be effective, even though it’s a mystery how it works — is as valid now as it

was in 1911. Others disagree.
210 complementary therapies The two most widely used methods that have been developed in this way are Provocation-Neutralisation and Enzyme- Potentiated Desensitisation.

Although these techniques are practised by doctors with a conventional medical training, they remain ‘outside the pale’ as far as orthodox medicine is concerned. The

controversies that surround them are discussed below.
Enzyme- Potentiated Desensitisation (EPD)
This technique has been developed by a British doctor, Dr Len McEwen, who began work on it in the 1960s. It is now practised in many parts of the world, as well as Britain,

including the United States, Germany and Italy.
EPD is used for a far wider range of problems than conventional immunotherapy, being given to people with food intolerance and chemical intolerance, as well as to those with

true allergies. This — along with the fact that it is unclear how it works —contributes to the controversies that surround it, because these conditions do not have the same

basic causes.
Dr McEwen began with the observation that, when immune cells are aroused during inflammation — whether caused by allergy or some other stimulus — they release large amounts of

an enzyme called beta-glucuronidase. This enzyme increases the immune response to the allergen or antigen that provoked the inflammation.
Dr McEwen experimented with injecting beta-glucuronidase into the skin, along with very small amounts of allergen, believing that in such circumstances the enzyme might have the

opposite effect, and reduce the immune reaction to the allergen. Eventually he discovered a combination of enzyme and allergen which seemed to have the desired effect.
EPD has been tested, in a rigorous scientific manner, and the results suggest that it can work for hayfever and asthma, as well as for childhood migraine and hyperactivity in

children when these are triggered by foods.
In one trial with hayfever patients, researchers measured the levels of anti-pollen IgE following EPD treatment, and it did not rise during the pollen season as it normally does

in those with hayfever. This kind of finding is impressive because it is unlikely to be due to placebo effect. Not all studies have produced positive results, however.
In addition, doctors using EPD claim that it is very effective for patients with allergies who have not done well on the standard course of immunotherapy injections (see p.

164). This fits in with other studies suggesting that the immune changes brought about by EPD are fundamentally different from those induced by traditional immunotherapy.
Patients with true food allergy have been given EPD, and while it does not enable them to eat their culprit food, it does
seem to reduce their reaction to accidental exposures.
Doctors in the Netherlands are using EPD as a treatment for people with Chronic Fatigue Syndrome (CFS), and report that it helps about 50% of patients.
One point in favour of EPD is that it uses very small amounts of allergen, and is therefore very safe — anaphylaxis has never occurred with this technique.
Provocation-Neutralisation
‘After following conventional methods [of immunotherapy] for thirteen years, I heard Carleton H. Lee deliver a paper on provocative testing in 1965, at a meeting of the American

College of Allergists in Chicago. I was naturally sceptical, but tried his suggestions when I returned to my office. The results can only be described as astounding. Many

patients with unresolved allergic problems responded markedly and rapidly. Many with resistant asthma or perennial allergic rhinitis improved greatly or cleared completely when

food injection therapy was added to their inhalant injection therapy.’ So wrote Dr Joseph B. Miller — a distinguished allergist and paediatrician, and a Professor of Medicine at

the University of Alabama, in 1972.
The technique which he learned from Carleton H. Lee was controversial then and, although Miller developed it with great care and precision during the years that followed, it

remains controversial now.
There are two elements in provocation - neutralisation: testing and treatment. Both are used for a wide range of problems — not just classical allergic diseases, but also food

intolerance and chemical intolerance. As with EPD (see left), this is one of the controversial aspects of the technique.
Although provocation-neutralisation involves an injection technique that looks, superficially, very much like conventional immunotherapy (see p. 164), there are several

important differences. Firstly, the allergen extract used (in the case of true allergies) is a very dilute extract, so that far less of the allergen is injected than in

conventional immunotherapy. Likewise, in the case of food intolerance and chemical intolerance, the extracts of the offending substance are used in highly dilute form.
Secondly, the idea of the neutralising dose — which is the central plank of provocation-neutralisation — is quite different from anything in conventional immunotherapy. Broadly

speaking, the conventional technique (see pp. 165-6) works by slowly reeducating the immune system with a gradually increasing dose of the allergen. Only after a succession of

injections does the immune system start to behave differently on encountering the allergen. By contrast, in provocation-neutralisation treatment, the neutralising dose is

claimed to have an instantaneous and direct effect on the body, ‘turning off’ symptoms that have already begun. This is the neutralisation aspect of the technique. The doctors

who practise this technique do not claim to know how the neutralising dose might work.
According to the theory of provocation-neutralisation, the strength of the extract that acts as a neutralising dose is specific for a particular allergen and a particular

person. It can only be worked out by a rather slow procedure involving a series of injections. These are intradermal injections – they place the allergen extract in the skin, at

a slightly deeper level than a skin-prick test. (For treatment, rather than testing, subcutaneous injections are used – these go deeper than intradermal injections, placing the

allergen extract just underneath the skin. Neither hurts very much.)
Ideally, the neutralising dose should be decided on by measuring the size of the wheal (a raised area of skin around the injection site), and whether it grows, stays the same

size, or disappears. The doctor or nurse carrying out the procedure can, in theory, work out the neutralising dose just by careful examination of the skin wheals.
However, it is part of the tradition of provocation-neutralisation techniques that verbal feedback from the patient is also taken into account – so if the patient says that an

injection has turned off the symptoms, that reinforces the belief that the neutralising dose has been found.
The problem with this aspect of provocation-neutralisation is that expectations, and the power of suggestion, can become involved. So if the doctor or nurse says ‘you may find

that this next injection makes the symptoms go away’, that is often exactly what happens – because the forces of placebo effect (see p. 233) come into play. Unfortunately,

verbal interactions such as this are a key aspect of the provocation-neutralisation procedure in many clinics.
Just the same hazard besets provocation - neutralisation if it is used to test for the existence of allergy or intolerance, because it is quite common for practitioners to tell

patients which allergen (or other offending substance) is being injected and to ask if any symptoms are provoked by the injection. This is not good practice – if someone expects

to react to a particular substance, they are quite likely to produce symptoms through purely psychological mechanisms (see pp. 232-3).
Quite apart from this, the question of allergy testing with provocation-neutralisation techniques is contentious, because the pioneers of the technique, such as Professor

Miller, never advocated using provocation - neutralisation in this way. Using it as a routine test for sensitivity reactions was a later development, and there are many doctors

today who, while they practise provocation-neutralisation as a treatment, say that it does not work well as a test for sensitivity reactions. While they agree that injecting a

dose
which is either stronger or weaker than the neutralising dose may provoke actual symptoms (this is the provocation aspect of the technique) they don’t think the reaction is

reliable enough to form the basis of a test for allergies. Nor do they think that using skin-wheal measurements alone (i.e. silent testing) turns the technique into an accurate

test for allergies. That is not what the provocation-neutralisation technique was designed for – it is about treatment, not testing.
The evidence from research
Recent research from the Nova Scotia Environmental Health Centre in Canada confirms that testing by provocation injections is not reliable. The subjects in this study were all

suffering fr= multiple chemical intolerance, a condition which – for one reasor or another – makes patients liable to develop symptoms at an,, time. No less than 70% of these

patients experienced symptoms in response to a dummy injection which contained none of the offending substance. Indeed, 15% of patients also produced a skin wheal in response to

some of the dummy injections, confirming that even this reaction may be subject to the power of suggestion (see pp. 232-3).
Looking just at the patients who did not react to the placebo injection (i.e. those least susceptible to suggestion) the test still did not yield any reliable result – a person

might react to one injection with a particular substance, but fail to react to a subsequent injection with the same substance. The authors concluded that their patients were ‘in

a state of heightened sensitivity as the result of the chronic irritation by various environmental components and other external and internal stressors’. In this state of

sensitivity. patients are so close to the brink all the time that the smallest thing can trigger symptoms. So the apparent reactions to the test injections were actually

determined by other factors – some psychological factors (including a psychological response to the prick of the needle) and some external ones, such as exposure to smells or

very small amounts of airborne chemicals.
Another recent research study, carried out by scientists at the University of California, confirmed the finding of the Nova Scotia team as regards testing. Although this study

did not set out to look at the use of the neutralising dose for treatment, some of the patients were given neutralising doses during the testing process and the researchers

observed that ‘in most cases a single neutralising injection relieved the symptoms’. This casual observation clearly needs to be confirmed by more rigorous testing. Oddly

enough, despite this positive observation about the neutralising doses, the overall conclusion of the researchers was to completely dismiss all aspects of

provocation-neutralisation as ‘the result of suggestion and chance’. This conclusion has been widely publicised in the United States as part of a general campaign against

provocation-neutralisation and doctors who practise it.
Other researchers have looked at treatment with neutralising doses, using stringent scientific methods (a double-blind placebo-controlled trial — see p. 90), and found that they

do work. In one such trial, patients with asthma. and allergies to dogs or cats, were treated with injections of the neutralising dose. They showed a reduction in the

sensitivity of their airways, as measured by objective tests. In another experiment, patients with perennial allergic rhinitis and an allergy to house-dust mite were studied,

and the neutralising dose was given as drops of allergen extract placed under the tongue (sublingual drops) – an alternative to injections. The blockage of the nose, as measured

by scientific tests, was reduced by the neutralising dose.
A great many more trials of this kind would be required to convince most doctors that provocation-neutralisation works.
Furthermore, the recent study from California – which observed a number of practitioners of provocation-neutralisation at work with their patients — showed that these

practitioners need to be a lot more rigorous and objective in their approach. However, the fact that provocation-neutralisation is often practised badly does not necessarily

mean that the basic technique is without any value. There are a great many level-headed doctors and patients who, while initially very sceptical about

provocation-neutralisation, have found it surprisingly effective – just as Professor Miller did back in 1965.
Deciding for yourself
So is provocation-neutralisation an option that is worth trying for your condition?
As regards testing, the answer is probably ‘no’. The most reliable tests are skin-prick tests or FAST blood tests for true allergies (see pp. 91-2), an elimination diet for food

intolerance (see p. 194), and avoidance followed by re-exposure (a challenge test) for chemical intolerance.
As regards treatment for true allergies, conventional immunotherapy has been far more thoroughly tested and, if you can get it (not easy in Britain — see p. 164), is probably a

better bet. It is definitely the best treatment for allergy to insect stings.
The major advantage that provocation-neutralisation has over conventional immunotherapy, in the case of true allergies, is that it is far safer. Because such small amounts of

allergen are used, anaphylactic reactions (see p. 58) don’t occur.
When it comes to treatment for food intolerance, complete avoidance of the problem food(s), for a period of a year or two, is usually a very effective treatment (see p. 77).

Other forms of treatment are only needed for people who find that they have
intolerance to a great many different foods (on the basis of an elimination diet, not kinesiology, blood tests and the like — see p. 93) and cannot devise an adequate diet from

the foods they are able to eat. For such people, provocation-neutralisation may be worth a try. Many patients feel that they have gained considerable help from this treatment.

They report suffering fewer symptoms and being able to return to a more nutritionally balanced diet.
In the case of chemical intolerance, the first line of treatment should be to avoid the substances concerned as far as possible, eat a good balanced diet, and take a vitamin and

mineral supplement if nutritional deficiencies are suspected. Treating any underlying hyperventilation (see pp. 226-9) can also help considerably. Only if there are persistent

symptoms, and you are sure these are not due to psychological causes, might provocation-neutralisation be worth a try. Some people with chemical intolerance do find it is

helpful, but whether this is a real effect, or simply placebo, remains uncertain.
If you decide to give provocation-neutralisation a try, find a practitioner who has good medical qualifications, who seems objective and sensible in their approach, and who

doesn’t make implausible claims for the technique. Take note of what other treatments the practitioner offers, and whether these seem rational or not – this is often a good

guide to the care and objectivity with which provocation - neutralisation is carried out.
Ask the doctor how he or she assesses the neutralising dose. and avoid anyone who does not use the traditional method of a series of injections combined with wheal measurement.

When the neutralising dose is being assessed, say that you would like it to be done ’single-blind’ – that is, you don’t want to be told anything about what is being injected.

Reporting how you feel to the doctor or nurse during the assessment is fine, but only mention really significant symptoms, or a very definite clearance of the symptoms, if this

occurs. These precautions will help you to be sure that you are getting something which is of genuine benefit, rather than just a very expensive form of placebo treatment.
I always wanted to be a doctor, and I enjoyed
medical school immensely, but once I became a
ell GP, I no longer felt quite so sure about what I was doing. It seemed clear to me that there were a lot of people coming to my surgery who I couldn’t do much for. And there

were others who, while I could treat their obvious medical problems with some success, remained distressed and were not coping well with life. Once I became a senior partner in

this practice, I experimented with having a counsellor come in for one session a week, and then an osteopath for the bad backs. It was popular with the patients, and I saw some

people improve enormously. Now we have stress-management classes too, and one of my colleagues has trained in acupuncture, which he uses for selected patients. We also use

elimination diets for patients with a lot of long-term problems like migraine. Overall, I think of it in terms of having more tools at our disposal - being able to tackle things

from a different angle when standard medicine isn’t hitting the spot.’
Geoffrey, a GP in the north of England, is typical of the reconciliation that is now beginning to occur between conventional medicine and alternative medicine. But he also has

plenty of criticisms to make of the alternative scene. ‘The idea that alternative medicine is “holistic” while conventional medicine isn’t, really raises my hackles. Most GPs

could be magnificently holistic if they had an hour with each patient as alternative therapists usually do. We have just 15 minutes, on average, and we have to pack a lot into

that - including our basic duty to eliminate the possibility of serious organic disease such as cancer. Time pressure is everything now, and it has squeezed the humanity out of

medicine, to a very large extent. But the potential for a holistic approach is there - most doctors have a tremendous store of wisdom and life
experience at their disposal, which could form the basis of a holistic approach to treatment if only there were more time to spend with each patient.’
It is in search of a more unhurried and all-embracing approach to treatment that many people turn to alternative medicine. Frequently, what they get out of the therapy has less

to do with the actual methods used, and still less with the theories behind those methods, but everything to do with spending a quiet hour with someone supportive and caring who

listens to all the complex concerns that surround any illness, gives reassurance or advice, or just offers a `safe space’ in which to talk about life’s difficulties.
Other people turn to alternative therapies due to a more serious disillusionment with orthodox medicine. When patients with inscrutable medical problems -such as persistent

unexplained diarrhoea, joint pain or chronic urticaria - are given a succession of different diagnoses by different doctors, they often lose faith entirely in modern medicine

and reject orthodox treatment in favour of alternatives. This is a great mistake. Modern medicine isn’t perfect, but that is only to be expected, because it is not a fixed body

of knowledge but a process - a continuing journey of questioning, investigation, discovery and improvement. Scientific medicine has come a tremendously long way from the state

of ignorance that prevailed two centuries ago, and it will undoubtedly go farther.
Conventional medicine has a great deal going for it - ask anyone over 50, with severe life-long asthma, what they think of treatment now compared to treatment in the 1950s or

early 1960s. You will hear a hymn of praise to the improvements in both drugs and drug delivery systems. Asthma is just one example -conventional medicine has a lot to offer for

all the classical allergic diseases. Alternative medicine should always be regarded as an adjunct to conventional treatment, not a replacement. That is why many doctors prefer

the term complementary medicine.
A third reason for using alternative medicine is a more philosophical one, a need to understand illness in some larger sense, often part of a general search for meaning in life.

Some types of alternative treatment attempt to offer metaphysical reasons for allergy -rather than the mundane explanations of antibodies and immune cells that are given in this

book - and this can be attractive to some people. There is no harm in this approach, which can prompt you to make a critical review of your life, look at unresolved emotional

issues, or reassess choices that are making you unhappy.
But not all illness, or worsening symptoms, can be explained by emotional causes, and the rigid belief that every illness must have a meaning can be damaging. It easily

degenerates into the wholesale psychologisation of illness, the kind of blame-the-victim mentality which can attribute hayfever to ‘Emotional congestion; fear of the calendar; a

belief in persecution; guilt’ and asthma in babies to ‘Fear of life; not wanting to be here’. Both these diagnoses are taken from the best-selling You
can Heal your Life by Louise Hay, which is very influential among some alternative therapists. This compulsive psychologisation of illness can be profoundly damaging, and if

your complementary therapist is preoccupied by ideas of this kind, you could find yourself on a very long guilt trip indeed.
Apart from the psychological aspects of alternative medicine, there is the question of whether it actually works in a practical sense - whether it provides more than just

emotional support and placebo effect (the benefit that comes from any treatment which you believe in). This is always the central question for scientific medicine in relation to

its own treatments,
and conventional doctors naturally apply the same criteria to alternative medicine. Most of this chapter is concerned with trying to answer that question.
Unfortunately, there are so many different kinds of alternative therapy available today that it is impossible to cover all of them in this book. To complicate matters further,

many complementary therapists now practise two or more different techniques, mixing them to
produce their own unique cocktail of diagnosis and treatment. This eclectic approach can span a remarkable range - you may find a therapist doing distinctly whacky stuff such as

iridology (looking at the eye to diagnose all illness - it has been tested and definitely doesn’t work), combined with something perfectly rational such as an elimination diet.

(The elimination diet might be presented as a ‘detox diet’, but it is actually being used to detect food intolerances.)
With new forms of therapy springing up all over the place, a healthy scepticism is a distinct asset for the consumer. Be sceptical about any diagnostic test or treatment that is

only being practised by one person in the country, or in the world - when doctors hit on something that works, they want other doctors to try it out. World exclusives in

medicine are usually suspect.
Avoid any practitioner who tells you to stop using your drugs without your doctor’s consent. Likewise, avoid those with a messianic gleam in their eye, an evident disregard for

logic or reasonable discussion, or an amazing cure that fixes everything from acne to AIDS. Very few of those who sell bogus cures and phoney diagnostic tests are complete

rogues. Most are nice people who are quite genuinely convinced that they have indeed found the answer to people’s problems. The powers of placebo effect (see p. 233) can sustain

such a conviction for a very long time.

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.

Various anti-allergy drugs
An allergic reaction is a lengthy, complex process, and the various anti-allergy drugs all work on different stages of that process. That is why it often makes sense to use several different drugs for the same allergic condition: they each tackle the problem in their own way.
Steroids (see p. 140) intervene at a very late stage, quelling the inflammation that follows on from an allergic reaction. Using a steroid is rather like calling the fire brigade to put out a fire, whereas using an antihistamine (see p. 138) is like having fire-proof doors, to prevent the fire spreading at an early stage. Cromoglycate-type drugs (see below) intervene at an even earlier stage. They are like basic fire prevention - teaching children not to play with matches, or fitting smoke detectors.
Anti - leukotnene drugs (see p. 149) work at roughly the same stage of the process as anti-histamines but tackle an entirely different aspect of the allergic reaction.
Cromoglycate-type drugs
These drugs are also referred to as mast-cell stabilisers or mast-cell Mockers.
There are three drugs in this group, sodium cromoglycate (also spelled cromoglicate), nedocromil sodium, and lodoxamide. All operate at an early stage of the allergic reaction, stopping it before it actually starts. They stabilise the outer membrane of the mast cells (see box on p. 12), which prevents the allergic response from occurring.
Some common brand names
Common brand names of cromoglycate-type drugs include:
inhalers - Cromogen Easi-Breathe, Intal, Tilade
eye drops - Hay-Crom, Opticrom, Rapitil, Vividrin, Viz-on nose sprays - Rynacrom, Vividrin
capsules - Nalcrom
This is a far more satisfactory way of dealing with an allergic reaction than trying to tackle it after the reaction has occurred. But from a purely practical point of view, it has a drawback. I order to work at all, these drugs must reach the mast cells in advance of the allergen. They are of very little use if taken after the allergic reaction has begun.
For those who are taking cromoglycate-type drugs on a regular schedule, several times a day, it is very important to be conscientious about taking them on time. This maintains the protective effect of the drug, without any gaps.
If you are using these drugs on an ‘as-needed’ basis, you should take them 30 minutes before an allergen is encountered. or 30 minutes before a bout of exercise, if they are being prescribed for exercise-induced asthma. (Note that children sometimes respond differently, getting protection from these drugs immediately.)
The effect of these drugs takes time to build up. You should take them regularly for at least four weeks before deciding whether they are helping you or not.
One point in favour of cromoglycate-type drugs is that they are extremely safe, with few or no side effects in most people. Sadly, they do not work for everyone. A fairly high percentage of children respond well to them, but the response rate is much lower for adults. Nevertheless, adult allergy sufferers, especially those who need steroids to control their symptoms, should always be given the opportunity to try out these drugs. When cromoglycate-type drugs do work, they are very effective and almost always trouble-free, so they are a good alternative to steroids.
Both sodium cromoglycate and nedocromil sodium are available in inhaler form for asthma (see p. 157). Sodium cromoglycate is also available as nose drops for hayfever and other nasal allergies.
All three drugs are available as eye drops. Recent evidence suggests that sodium cromoglycate drops are less effective than the other two, particularly for the treatment of severe allergic conjunctivitis (inflammation of the eye).
Sodium cromoglycate is available in capsule form for food allergy. Note that these capsules are of very limited value in food allergy, and are certainly not a substitute for food avoidance. They do reduce sensitivity a little and can sometimes be helpful for those with multiple food allergies (see p. 67).
Side effects
There are no serious side effects at all for nedocromil sodium. cromoglycate can, very rarely, cause joint pain and swelling. An allergic reaction to the drug itself is even more uncommon. Stop taking the drug and see your doctor promptly if either of these occurs.
The only other side effects that have occasionally been reported are headache, nausea and vomiting. None of these indicates any damaging effect by the drugs – they are all minor side effects.
Eye drops containing these drugs may cause stinging and burning when inserted, but this is a minor side effect and usually wears off. Flushing and dizziness have sometimes been reported with lodoxamide eye drops.
Nose drops may also cause local irritation. This could be due to the drug itself, in which case it is a minor side effect. Alternatively, the irritation may be due to the preservative used or some other non-drug ingredient (see box on p. 33).
Occasionally cromoglycate nose drops cause bronchospasm – contraction of the airway muscles – but this tends to wear off quite quickly. Bronchospasm can also occur when cromoglycate-type drugs are inhaled (see p. 157).
Anti - leu kotriene drugs
These drugs, which have a set of very specific effects (see p. 159), were originally designed to treat asthma. Their potential for treating other allergic diseases is currently being explored:
•    Several studies show that they work well for perennial allergic rhinitis brought on by allergens such as house-dust mite. They also have some effect on hayfever, but standard treatment (such as antihistamines plus a steroid spray for the nose) is more effective.
•    They are especially useful for both rhinitis and asthma in patients suffering from triad (see box on p. 28). Research shows that they also reduce asthmatic reactions to very small test doses of aspirin, but they don’t give protection against anaphylaxis brought on by normal doses.
•    They have also been used successfully in cases of chronic urticaria and for some patients with delayed pressure urticaria. It seems plausible that they would also be helpful for chronic urticarla linked to aspirin sensitivity.
•    Preliminary trials suggest that these drugs might be useful in atopic eczema. Some studies show a very good response that allows a reduction in steroid creams.
•    Montelukast works very well for eosinophilic gastroenteritis and eosinophilic oesophagitis (see p. 72), according to some new studies.
For side effects of these drugs see pp. 159-60.
Anti-IgE drugs
Since the antibody IgE (see box on p. 12) is such a crucial player in allergic reactions, developing drugs that disable this antibody should help allergy sufferers. The first such drug is omalizumab (brand name Xolair) which was licensed for use in the United States in 2003. It is expected to become available in Britain some time in the next few years.
Omalizumab binds to IgE antibodies and stops them from interacting with mast cells, so blocking any allergic reaction. The drug is given as a ‘depot injection’, just under the skin, every 2-4 weeks. It is gradually released from the injection site and moves around the body in the blood, mopping up IgE molecules.
At present, omalizumab is used for severe hayfever and for people with asthma who are not responding well to the usual treatments. It is only worth using if there is clear evidence that allergies play a part in the asthma. Patients who use omalizumab are often able to reduce their dose of inhaled steroids – and they suffer fewer serious asthma attacks and have better lung function. Some patients can even stop using steroids completely.
Other anti-IgE drugs are in the pipeline. Pilot studies show that one works very well for peanut allergy: after just four injections, sensitivity to the allergen falls sharply, reducing the risk of anaphylaxis from traces of peanut eaten accidentally.
More powerful anti-allergy drugs
Occasionally people with severe allergies, who are on constant high doses of steroid tablets, or who fail to respond to steroids, need treatment with powerful anti-inflammatory drugs, such as methotrexate or cyclosporin. These suppress the immune system, and extremely careful monitoring for side effects is needed.
Adrenaline (epinephrine)
Anyone who has suffered anaphylactic shock (see p. 58) should be carrying a special syringe, called an auto-injector, loaded with adrenaline. The injector is very simple to operate and is designed for emergencies. Most allergy sufferers, even children, can give themselves the injection – or a parent or other adult can give it.
Some asthmatics, and those with food allergy who suffer swelling of the throat, may be given adrenaline in inhaler form as well (see pp. 155-6). This can be useful as an additional treatment but it’s definitely not a substitute for an injector.
See pp. 98-9 for instructions on using adrenaline in a crisis.
Wherever you go, take your injector with you. Always keep it close at hand: you need to be able to use it within minutes of the allergic reaction starting. You may be unable to speak (and therefore unable to ask someone else to fetch it) quite soon after the attack begins. The injector must never be refrigerated. It can also be damaged by sunlight and excess heat.
If you live in the countryside or in an area with a poor ambulance sevice, or if you are going camping or hiking somewhere remote, ask your doctor for a second injector, or one that can deliver multiple injections. Also ask about the maximum number of injections that can be given, and never exceed this total. Some doctors believe everyone should have two injectors, just in case the first dose doesn’t do the trick and help is slow in coming.
It is vital that you are shown exactly how to use the auto-injector. Canadian researchers discovered that only one in four
Some common brand names
Common brand names of adrenaline preparations include: auto-injectors – Anapen, EpiPen
inhalers – AsthmaHaler Mist, Bronkaid, Epiphrine
health professionals got the technique correct when demonstrating how to use an auto-injector In this study, pharmacists were much the best as regards accurate instructions. Dummy injectors are useful for training purposes and most pharmacies have them.
When the adrenaline auto-injectors expire, they can be very useful for practising with, or for showing a new baby-sitter or teacher – practise on an orange or grapefruit.
If you are taking beta-blockers (e.g. for a heart condition or anxiety), adrenaline may not have much effect.
Heavy daily use of beta-2 relievers for asthma (see p. 152) will also make adrenaline less effective when you need it.
Side effects
The important side effects of adrenaline involve the heart. Anyone with a heart condition should be given special advice in advance by their doctor about using adrenaline. The same goes for people with diabetes, hyperthyroidism or high blood pressure, and anyone taking tricyclic anti-depressants. There are quite a few minor side effects from adrenaline, such as anxiety, trembling, nausea. sweating, dizziness and cold extremities. These soon wear off.
Drugs that can make you worse
Aspirin and its relatives have a very bad effect on some people with rhinitis and/or asthma (see box on p. 151). Unfortunately, recent research shows that paracetamol is not safe either. It makes asthma more likely to develop in those who do not yet have the disease, and increases the severity of asthma symptoms for those who do. Unlike aspirin, paracetamol affects everyone, because it lowers the levels of a natural antioxidant, called glutathione, which the body makes to protect the lungs from oxidants. The greatest effects are seen in people who take paracetamol regularly (once a week or more), but even an occasional dose makes some difference.
All the other drugs that can make you worse are prescription drugs, and your doctor should be alert to the dangers. But doctors are overworked and sometimes forget, so it is sensible to know about the risks for yourself. If you have any doubt about the drugs you are taking, ask a pharmacist.
Beta-blockers are a major hazard for people with allergies. They can make the airways contract, and can bring on a serious asthma attack. They also make anaphylaxis more likely in someone who already has allergic reactions (see p. 59) and they increase the risk of a severe reaction to
immunotherapy (see p. 166) or skin-prick tests (see p. 91). Beta-blockers are prescribed for high blood pressure, angina and other heart problems, migraine and thyroid disease. There are alternative drugs in all cases. Sometimes asthma develops in people who have been taking beta-blockers for years. The beta-blockers are not responsible for this, but once asthma has begun, they will make symptoms worse. Eye drops for the treatment of glaucoma may also contain beta-blockers and can have a bad effect on asthmatics.
ACE inhibitors, used for heart conditions, may cause a cough and airway narrowing. They may also increase the risk of a severe reaction to immunotherapy.
Female hormones affect asthmatics, so taking the contraceptive pill or hormone replacement therapy (HRT) may make asthma worse. Progesterone-only contraceptive pills tend to cause fewer problems.
The drug isoniazid (INH), prescribed for tuberculosis, makes the body far more susceptible to histamine in foods (see p. 200).
An allergic reaction to a specific drug (e.g. penicillin) can also occur in some people, resulting in urticaria, or even anaphylactic shock.
Aspirin sensitivity
Aspirin sensitivity is not an allergic reaction, because neither IgE nor mast cells are involved. What causes this problem is a metabolic abnormality — a malfunction in one aspect of the body’s chemistry. The details of this are very complicated: you may want to skip the next three paragraphs and
simply read about how to cope with the problem.
The exact nature of aspirin sensitivity is still far from clear, but it seems to involve a relatively poor production of prostaglandins, combined with a plentiful production of leukotrienes. Both these substances are messenger chemicals which, broadly speaking, promote inflammation. But the details of their pro-inflammatory activities differ. It seems that, ideally, the body should have a harmonious balance between the two, and an imbalance produces problems.
Both prostaglandins and leukotrienes are manufactured from certain fats that are found in the diet. These fats, the raw materials, are worked on initially by two different enzymes — one that leads to the production of prostaglandins and another that leads to the production of leukotrienes.
If one of these enzymes is defective, it may mean that the other is oversupplied with raw materials, resulting in a serious imbalance between prostaglandins and leukotrienes. In those with aspirin sensitivity, or at risk of developing aspirin sensitivity, the enzyme that produces prostaglandins seems to be defective.
Even in the absence of aspirin, this imbalance in the production of prostaglandins and leukotrienes causes problems. It leads to symptoms such as chronic urticaria (see p. 51) or rhinitis, nasal polyps and asthma (a cluster of symptoms that is commonly called triad — see box on p. 28).
Taking aspirin can make the imbalance between prostaglandins and leukotrienes even worse in a person with this underlying abnormality. Aspirin exerts its painkilling effects by disabling the main prostaglandin-making enzyme — the enzyme that is already defective.
When someone with aspirin sensitivity takes aspirin, they may suffer worsening asthma, a severe asthma attack or — the worst-case scenario —collapse. This is a potentially fatal reaction, similar to anaphylaxis, requiring emergency medical treatment (see p. 101).
The greatest puzzle about aspirin sensitivity is why it often takes so long to develop in someone who already has the symptoms of triad —indicating the basic metabolic abnormality. It may be as much as 20 years from when someone has their first triad symptoms to when they begin reacting badly to aspirin.
If you have triad symptoms already, but no aspirin sensitivity yet, what should you do? Unfortunately, there are no safe tests for aspirin sensitivity at present — taking a small dose of aspirin and seeing what happens is very hazardous. It is probably best to assume that you are going to become sensitive to aspirin at some stage, and avoid all aspirin and aspirin-like drugs. Caution is the best plan here because aspirin sensitivity can come on very suddenly, and be life-threatening the very first time it occurs. Note
that some triad sufferers have polyps and rhinitis but no asthma until they actually develop aspirin sensitivity — a dose of aspirin suddenly brings on their first asthma attack plus other symptoms of aspirin sensitivity.
Avoiding aspirin itself is not difficult, but aspirin-like drugs pose more of a problem. Every year there are a number of deaths from these drugs. Some cases occur because a busy doctor momentarily forgets that a patient should not take these drugs. The drugs that need to be avoided are all known as non-steroidal anti-inflammatory drugs (NSAIDs), COX-1 inhibitors or COX-2 inhibitors. However you will not see any of these names on the packet. These drugs are very widely used for pain relief (e.g. in headache and backache remedies such as Nurofen), for the treatment of arthritis, and for several other inflammatory diseases.
There are dozens of non-steroidal anti-inflammatory drugs available, and many are sold under several different brand names. The list grows every year, as new drugs or new brands are launched. The only way to avoid these drugs is to be very cautious:
•    When buying any cold- or flu-remedies, painkillers, medicines for sprains or sports injuries (including those you apply directly to the skin), headache tablets or migraine tablets, always buy them at a chemist’s shop rather than a supermarket, and check with the pharmacist that they do not contain aspirin or aspirin-like drugs.
•    Be cautious also about remedies for an upset stomach. A few (e.g. Alka-Seltzer) contain aspirin.
•    Don’t take any drugs unless you are 100% sure of what they contain. Remember that the ingredients of a familiar brand name can sometimes change — read the label every time.
•    When a doctor prescribes any new drug, always mention that you are sensitive to aspirin, or that you have triad symptoms. Alternatively, check with the pharmacist when the prescription is filled.
•    Aspirin-free painkillers almost always contain paracetamol, a drug which can cause a severe reaction (similar to the collapse induced by aspirin itself) in about 5% of those with aspirin sensitivity. If you are taking paracetamol for the first time, start with half a tablet. Be sure that, for the next 2-3 hours, you have a way of getting to hospital quickly should you start to feel ill. (Note that paracetamol has another entirely separate effect, increasing the severity of asthma, and it is best not to take it too often — see box on p. 150.)
Avoiding all aspirin-like drugs will prevent you having anaphylaxis or severe attacks of asthma. Unfortunately, triad symptoms will not go away however careful you are about avoiding aspirin.
It is well worth trying the new anti-leukotriene drugs (see p. 149), especially if you have aspirin-induced asthma. They seem to help with triad symptoms by curtailing the activities of leukotrienes and so redressing the balance between leukotrienes and prostaglandins.

Antihistamines and Allergy

Antihistamines were first introduced in 1947, and are very widely used, so their safety — at least in the case of the older antihistamines — is beyond doubt. Most of the antihistamines have no major ill effects, and no one should feel concerned about taking them. At worst they produce some rather annoying minor side effects, such as drowsiness, which often wear off in time.

These drugs are particularly valuable for hayfever and other allergies in the nose (perennial allergic rhinitis). They are also used for chronic urticaria, sometimes in combination with anotherhistamine-blocking drug — see p. 53.

Antihistamines are not much used for asthma. They have relatively little effect, probably because so many other messenger chemicals are involved in an asthma attack. However, doctors in Japan do use antihistamines for asthma, and it is possible that people of Asiatic origin react differently to them.

Only one antihistamine, ketotifen, is widely used for asthma in the West, and this has other effects besides blocking histamine (see p. 159). A new role may soon develop for antihistamines in thetreatment of asthma, combined with anti-leukotriene drugs (see p. 159).

If you suffer from anaphylaxis you might be given antihistamines in a liquid or chewable form, for use in an emergency. These are not enough in themselves to treat this dangerous condition - you must have an adrenaline injector (see p. 150).

In the past, some doctors prescribed antihistamines for atopic eczema, mainly for their sedative effect(see p. 139) which was thought to help children to sleep better and scratch less at night. This treatment has largely gone out of favour, because its value is in doubt. But a recent study has revealed that the non-sedating antihistamine cetirizine may be useful for very young children with atopic eczema, not only in treating their skin, but also in reducing the chance of them developing asthma (see p. 249).

Most people take their antihistamines in tablet or capsule form. Syrups and sugar-free elixirs areavailable for children.

Antihistamines can also be applied directly, in the form of nasal sprays or eye drops. These are mainlyused to treat hayfever and the conjunctivitis (inflammation of the eye) which often accompanies it.Levocabastine (brand name Livostin) is particularly effective for the eyes.

Antihistamine creams are also sold, without prescription, for the treatment of insect bites - i.e. thenormal non-allergic reaction to such bites. These creams are not recommended for atopic eczema or otherallergic conditions affecting the skin. Not only are they unlikely to help, but they may make mattersworse because, with regular use, skin sensitisation to the antihistamine occurs very readily (see pp.54-5).
Some common brand names

Common brand names include: non-sedating antihistamines - Clarityn, Semprex, Zirtek; Mistamine, Mizollen, Telfast, Terfenadine. Thefirst three are available without prescription.

older (sedating) antihistamines — Atarax, Dimotane, Optimine, Periactin, Piriton, Tavegil, Vallergan eye drops — Emadine, Livostin, Optilast nasal sprays — Livostin, Rhinolast

How antihistamines work
Of the messenger chemicals released when an allergic reaction occurs, the most important is histamine.

This does its work by attaching to specialised receptors in certain parts of the body, and so

triggering various reactions (see box on p. 12). The action of antihistamines is very simple: they bind

to the same receptors as histamine, but they do not trigger any reaction. Histamine cannot bind to the

receptor because the antihistamine is already there.
Unfortunately, the reverse is also true: if the histamine is already there, the antihistamine cannot

elbow it off the receptor, which is why it is important to take the antihistamine well before the

allergen is encountered. Taking antihistamines at the first sign of a snuffle or itch can also work,

but the effects will not be nearly as good as taking them in anticipation of an exposure.
The best approach to treating hayfever, for example, is to start taking the antihistamines at least a

week before the pollen season begins, and preferably two to three weeks before. You should then take

them continuously until it is over. This will make a huge difference to the degree of symptom control

you achieve.
Side effects
The older types of antihistamine, such as chlorphenamine (brand name, Rriton) are relatively

non-specific in their effects – they bind to several different kinds of receptors, not just those for

histamine. As a result they can have some unwanted effects, such as causing drowsiness and poor

coordination. While these sedative effects are no cause for concern in themselves, they can, of course,

be hazardous if you work with dangerous machinery or drive. Avoid both until you are sure how you react

to the antihistamine. Note that the effects of alcohol may be increased.
Very occasionally antihistamines have the opposite effect, causing stimulation rather than sedation;

this is most likely to occur in children and old people. Lowering the dose may solve the problem.
The other possible side effects of the older antihistamines –all of which are minor ones – are

headache, dry mouth, blurred vision, difficulty in passing urine, nervousness, shaky hands, upset

stomach or diarrhoea. A few men suffer impotence while taking antihistamines, but this disappears when

the drug is stopped.
The minor side effects of antihistamines, including drowsiness, often wear off after a while, although

the benefits of the drug remain. So it is worthwhile persisting with an antihistamine, even if it

causes some problems at first. Many people experience side effects from certain antihistamines but not

from others, so try several different types to find one that suits you.
The problem of drowsiness has been reduced, in recent years, thanks to the development of new drugs

that are far more
specific for histamine receptors, the non-sedating antihistamines. A few people do get drowsy even with

these drugs. Again, the effects vary from one drug to another, so if the first one disagrees with you,

try a different one.
It is worth noting – since some people may still have the odd packet in their medicine cabinet – that

two of the non-sedating antihistamines that were available without prescription a few years ago proved

to be unsafe for a small minority of people. One was astemizole (brand names: Hismanal, Pollon-eze),

which has now been withdrawn from use altogether in Britain. The other was terfenadine (brand names:

Triludan, Seldane, Terfenadine) which is still available, but only on prescription.
There are several special precautions relating to terfenadine:
• Never exceed the correct dose.
• If you have ever had any kind of heart problem, talk to your doctor before taking terfenadine.
• Stop taking the drug if you have palpitations, or if you feel faint; see your doctor promptly.
• Do not take terfenadine if you are taking the antibiotic erythromycin, or anti-fungal drugs

such as ketoconazole (Nizoral) or fluconazole (Diflucan), used to treat vaginal thrush.
• Do not take terfenadine if you have liver disease.
• Do not drink grapefruit juice while taking terfenadine: something found naturally in grapefruit

interacts unpleasantly with this antihistamine.
In addition to these special precautions concerning terfenadine, any antihistamine should be treated

with caution by those suffering from epilepsy, Parkinson’s disease, glaucoma, prostate enlargement,

kidney problems, urinary retention, a gastric ulcer, a thyroid disorder, porphyria or liver disease.

Check with your doctor before taking antihistamines if you have any of these conditions.
It may be inadvisable to use antihistamines if you are taking sleeping tablets, anti-depressants or

anti-anxiety drugs – again, see your doctor.
Stop taking antihistamines if you suffer any unusual kind of rash, or if your skin becomes more

sensitive to sunlight.
If you are breast-feeding, note that, because they go through into the milk, the older antihistamines

may make the baby sleepy. However, they do no harm.
Rescue treatment
Most antihistamines perform very badly if you take them once the allergic reaction has set in, but

acrivastine (Semprex) can be good in these circumstances and is non-sedating. No prescription is

required for this drug.
possibly identify all major side effects. We vary in our response to drugs, because we are all so

different at the chemical and cellular level. A drug might have a serious side effect that only affects

one person in 10,000, and no safety trial can hope to identify such a rare response. Only when a drug

is released, and becomes widely used, do such side effects come to light. Other unanticipated side

effects can sometimes arise when people taking the new drug are much older than those in the safety

trials, or belong to a different ethnic group with different susceptibilities. Combining the drug with

certain other drugs can also be a potential source of trouble, although pharmaceutical experts can

often predict such problems from a detailed knowledge of the chemistry of drugs and how they are broken

down in the body. Side effects that take several years to develop - more than the timespan of most

safety trials - will also fail to show up until the drug has been released.
All this may sound very alarming, but in fact severe reactions to new drugs are not that common. And

there are various safety nets in place - doctors keep a close eye on patients taking new drugs, and a

special reporting system ensures that, if unexpected side effects do show up, the information is

quickly shared with others in the medical community.
In order to relate the information here to a particular medicine that you take, you need to know what

drug category it belongs to. Does your inhaler contain a beta-2 reliever, a steroid, a cromoglycatetype

drug or an anti-cholinergic, for example? If you are not sure, ask your pharmacist.
Those are the category names for drugs: they denote families of drugs which are similar chemically
and work in roughly the same way. Within each category, or family, there are a number of individual

drugs. The individual drugs should, ideally, have a standard internationally agreed name - this is

known as the generic name. Unfortunately, a few of the drugs used for allergies and asthma have more

than one generic name - salbutamol is known as albuterol in some parts of the world, and adrenaline is called epinephrine.

Finally there are the brand names, which are the ones most patients are familiar with. These are always

shown with a capital letter, unlike the generic names. Long-established drugs are usually made by

several different pharmaceutical companies, and therefore marketed under several different brand names.

A newer drug, which is still covered by the patent of the pharmaceutical company that developed it,

will be sold under only one brand name.

The issue of brand names is important, because a different brand name might make you think you are taking a different drug, when in fact it is exactly the same drug being marketed in a different guise.If you have suffered side effects from a particular drug in the past, and wish to avoid it in future, take note of its generic name, rather than its brand name. Sometimes the generic name is used as the brand name, in what are called generic drugs. These arerelatively inexpensive copies of popular drug brands -they are just the same chemically, but they costless because there is no advertising of the brand to doctors, and profit margins have been cut to aminimum. In order to reduce National Health Service costs, doctors are now asked to prescribe generic drugs whenever possible.