Posts Tagged ‘Histamine’

abciximab A monoclonal antibody that inhibits platelet aggregation and thrombus formation. Used as an adjunct to heparin in percutaneous transluminal coronary angioplasty under expert supervision. (ReoPro).
glaucoma, as it decreases intraocular pres    9 sure by reducing formation of aqueous humour. It has also been used in epilepsy. Dose: 250 nig-1 g daily. In severe conditions it may be given in similar doses by i.v. injection. Side-effects are drowsiness, gastrointestinal disturbances and paraesthesia. (Dianiox). See page 138 and Table 16.
acamprosate An analogue of GAGA used in alcoholism. It assists in the maintenance of abstinence in alcohol-dependence, but prolonged treatment for a year may be required. Dose: 666 mg 3 times a day. (Campral).
acarbose An inhibitor of alpha-glucosidase, the enzyme that converts dietary carbohydrates to soluble sugars. Used in noninsulin-dependent-diabetes to reduce hyperglycaemic peaks after food. Dose: 50 mg daily initially, rising to 150 mg daily if required. Side-effects are flatulence and diarrhoea; a hypoglycaemic reaction can be treated with oral glucose. (Glucobay). See page 131 and Table 13.
ACE inhibitors See angiotensin-converting enzyme inhibitors.
acebutolol A beta-adrenergic blocking agent with the actions, uses and side-effects of propranolol, but with a more cardioselective effect and less likely to cause bronchospasm.
Dose: in hypertension, 400-800 mg daily; in severe angina, up to 1.2 g daily. It is contraindicated in cardiogenic shock, atrioventricular-block and heart failure. Care is necessary in obstructive airway disease and renal failure (Sectral). See page 148 and Table 21.
aceclofenec A non-steroidal anti-inflammatorydrug (NSAID) used for the relief of pain in arthritic and rheumatoid conditions. Dose: 200 mg daily. (Preservex). See page 131 and Table 29.
acemetacin A derivative of indomethacin with similar actions and uses, but said to be better tolerated.
Dose: 120-180 ing daily. (Finflex). See page 165 and ‘[’able 29.
acetazolamide An inhibitor of the enzyme carbonic anhydrase that has been given as a mild diuretic, as it increases the excretion of bicarbonate. Now used mainly in mild
acetomenaphthone A synthetic form of vitamin K, formerly used in prothrombin deficiency. Menadiol and phytonienadione are now preferred. Acetoinenaphtlione is present in some chilblain preparations.
acetylcholine The neurotransmitter of the parasympathetic nervous system. A 1% solution is sometimes used as a miotic to obtain rapid contraction of the pupil after cataract surgery. (Miochol).
acetylcysteine A mucolytic agent used as eye drops 5% in tear deficiency. Of value in the early treatment (10-15 hours) ofparacetarnol poisoning.
Dose: initially 150 nig/kg by slow i.v. injection, followed by smaller doses up to a total dose of 300 mg/kg over 20 hours. It is inef1ictive, and possibly harmful, if given at a later stage. (Parvolex). See methionine.
acetylsalicylic acid See aspirin. aciclovir See acyclovir.
acipimox A derivative of nicotinic acid used in hypercholesterolaemia.
Dose: 500–750 mg daily. Side-effects are hushing, erythema, nausea and malaise. (Olbetani). See page 146 and Table 20.
acitretin A vitamin A derivative (retinol) used in severe psoriasis resistant to other treatment.
Dose: 20-30 mg daily. Teratogenic - see specialist literature. (Neotigason).
aclarubicin An anthracene cytotoxic agent of the doxorubicin type used in resistant acute non-lymphatic leukaemia. (Aclacin). See specialist literature.
acrivastine one of the newer antihistamines. It is less likely to cause drowsiness, as it does not cross the blood-brain barrier to any great extent, but is correspondingly less effective in non-allergic pruritus. Dose: 24 mg daily. (Semprex). See
page 110 and Table 2.

dimethicone Activated dimethicone is an antifoaming agent, said to reduce flatulence and protect mucous
membranes. It is a constituent of many antacid preparations. It is also present in some water-repellent skin creams.
dipipanana A rapidly acting morphine-like analgesic of value in the sever rain 4 to -1 dk–
Dose: 30-3450 mg (fail),, but it is usually• given in association with cyclizine as Diconal. The side-effects are similar to those of morphine.
dipivefrine A pro-drug that is converted into adrenaline after absorption. It is used
in chronic open angled- glaucoma as eye
drops (0.1%). (Propine). See page 138 and Table 16.
dimethylsulphoxide (DMSO) An organic liquid, it has been used for the symptomatic relief of interstitial cystitis
(Hunner’s ulcer) by the bladder instillation of 50 ml of a 50% solution. (Rimso-50).
dinoprost Prostaglandin F,.. It has actions and uses similar to dinoprostone.
(Prostin 112).
dinoprostone A synthetic form of prostaglandin E,. It has been used to initiate contractions of the pregnant uterus. Dose: 500 pg orally to induce labour, repeated if necessary at hourly intervals; as vaginal tablets or gel, 3 mg. Side-effects are nausea, diarrhoea, shivering and dizziness. (Prostin E2; Prepidil).
dioctyl sodium sulphosuccinate See dOCUSalC.
diodone injection A solution of a complex organic iodine compound, used as a contrast agent in X-ray examination of kidneys and ureters.
diphenhydramine One of the early antihistamines, with a more sedative action, and use(] in the temporary relief of insomnia. Dose: 10-25 trig. (Medinex. Nytol). It is also present in some cough preparations and nasal decongestants.
diphenoxylate A derivative that resembles codeine III reducing intestinal activity. It is used for the symptomatic relief of diarrhoea, and is usually given with a small dose of atropine to discourage excessive dosage and to reduce the risk of dependence. Dose: 10 mg initially, then 5 nig every 6 hours as required. (Lomotil;’Fropergen).
diphenylpyraline An antihistamine used as .I decongestant in colds and sinusitis. Present in Eskornadc.
dipyridamole An inhibitor of thrombus formation by reducing the adhesiveness of blood platelets in the arterial circulation. Dose: 300-600 mg daily before food. s I
ide-effects include nausea, diarrhoea and headache. (Persantill).
disodium cromoglycate See sodium cromoglycatc.
disodium etidronate See etidronate. disodium pamidronate See pamidronate.
disopyramide A quinidine-like drug used in the treatment of cardiac arrhythmias especially after myocardial infarction. Dose: 300-800 mg daily; dose by slow i.v. injection under ECG cover, 2 nig/kg up to 150 mg, followed by oral therapy as soon as possible. By its anticholinergic action care is necessary in glaucoma and prostatic enlargement. Contraindicated in heart block. (Dirythmin; Rythmodan). See page 1;6 and “fable 24.
distigmine An inhibitor of cholinesterase similar to neostigmine but with a longer action.
Dose: in the control of myasthenia gravis 5-20 mg as a single morning dose before breakfast; in urinary retention after surgery, 5 trig daily. It is sometimes used in neurogenic bladder disorders. Side-effects are nausea, abdominal cramp, diarrhoea and weakness. (Ubretid).
disulfiram When taken with even small amounts of alcohol, disulfiram permits the accumulation of acetaldehyde in the body, with side-effects such a flushing, giddiness, vomiting and headache that may be severe. Distilfiram is used in chronic alcoholism, but prolonged treatment and co-operation of the patient are essential.

Dose: after at least 24 alcohol free hours: 800 nig on the first day, falling over 5 days to 100-200 mg daily. Acute confusion may occur if given at the same time as tucLro-
llidazole. (Antabuse).
dithranol Synthetic compound used locally in the treatment of psoriasis. It is a powerful irritant, and treatment should be commenced with a simple ointment or zinc paste containing 0.1% ofdithranol, gradually increased to 1% if well tolerated. Higher concentrations are sometimes used in ’short -contact -time’ therapy.
Dose: 100 mg/m’ by i.v. infusion over
I hour. Rapid and severe hypersensitivity reactions (hypotension, bronchospasm) may occur, and treatment must be irrnediat4y available. Reaction risks may be reduced by premedication with jexalnetha&one given the day before treatment and continued for 5 days. Rash, pruritus and neutropenia may occur, and blood counts and liver function tests are necessary. (Taxotere). See page 122 and Table 8.
docusate A surface-active agent used as a faeces -softening laxative.
Dose: ill, to 500 nig daily. (Dioctyl).
diuretics The most widely used group of diuretics is the thiazides, represented by bendrofluazide (see page 14I ). They act mainly by increasing the excretion of
sodium by inhibiting its re-absorption by the distal tubule of the kidney, and evoke a rapid response which may persist over 12-24 hours, although some, such as chlorthalidone, have a still longer action. They are given in mild cardiac failure, oedema and in hypertension, but in more severe conditions, and in pulmonary occlema, the more powerful ‘loop’ diuretics, such as frusemide, which act at a different point, are preferred. A side-effect of some thiazides is an increase in the excretion of potassium which may require the use of potassium supplements or a change to a potassium sparing diuretic such as trianiterene. Spironolactone, an aldosterone antagonist, is a more powerful diuretic, of value in resistant oedema. Osmotic diuretics such as mannitol are used mainly in cerebral oedema. Simple diuretics such as potas slum citrate arc mainly used to alkalize the urine and promote diuresis in cystitis and similar conditions. See page 141 and Table 18.
dobutamine A sympathomimetic agent similar to isoprenaline, but with a more selective stimulant action on the beta, receptors in the heart. It increases cardiac contractility but is less likely to cause tachycardia. Useful in acute heart failure and cardiogenic and septic shock. Dose: 2.5-5 pg/kg/min by i.v, infusion, carefully adjusted to need. (Dobutr= Posiject). See page 141 and Table 18.
docetaxel A potent cytotoxic agent derived from the Pacific Yew. Used in advanced breast cancer resistant to other therapy.
domperidone An antiemetic that functions as a dopamine antagonist, as it prevents dopamine from reaching the receptors in the chemoreceptor trigger zone (see antiemetics). It is mainly of value in the severe nausea and vomiting caused by cytotoxic drugs, and is also useful in fum clonal dyspepsia. It is of little value in postoperative and travel sickness.
Dose: 10-20 mg 4-8-hourly; 30-60 nig by suppository. Sedative side-effects are infrequent, as domperidone does not cross the blood-brain barrier. (Motilium). See page 77.
donepezil A reversible inhibitor of anti-cholinesterase. Alzheimer’s disease is linked with a deficiency of acetylcholine in the brain, and donepezil may relieve sonic of the symptoms of that disease by increasing brain acetylcholine.
Dose: 5-10 mg at night. Diarrhoea and muscle cramps are side-effects. (Aricept ).
dopamine A sympathomimetic agent with actions and uses similar to dobutamine. Dose: 2.5-10 pg/kg/min by slow i.v. infusion. Careful control ofdose is essential, as dopamine may cause vasoconstriction with higher doses and increase the risk of heart failure. (Intropin). Dopamine is also a central neurotransinifter, and a deficiency is associated with parkinsonism. See levodopa, page 141 and “table 18.
dopexamine A short-acting drug of the dopamine type but with a more powerful action on the 0,-receptors. It is used in heart failure during cardiac surgery.

cephamandole A cephalosporin more resistant to inactivation by penicillinases. It is of value in serious infections resistant to other antibiotics.
Dose: 2-12 g daily by i.m. or i.v. injection. : Kellidol). See page 248 and Table 34.
cephazolin A cephalosporin with the
general properties of the group.
Dose: 1-12 g daily by injection. (Kefzol). See page 248 and Table 34.
cephradine A cephalosporin active orally as well as by injection.
Dose: 1-2 g orally daily; in severe infeclions 2–8g daily by injection. (Velosef). See page 248 .
certoparin A low molecular weight form of heparin. Used in prophylaxis of venous thromboembolism.
Dose: 3000 units once a day by s.c. injection (1-2 hours before surgery) for 7-10 days. (Alphaparin). See enoxaparin.
cetirizine A slower-acting antihistamine with reduced sedative effects, as it does not pass the blood-brain barrier to any extent. The anti-cholinergic side-effects are also reduced.
Dose: 10 nigat night. (’Lirtels). See page 110 and Table 2.
cetrinnide A detergent with some antiseptic properties. It is used chiefly in association with chlorhexidine.
charcoal Activated charcoal is a powerful adsorbent, and is used in the treatment of overdose or poisoning by many toxic drugs by preventing further absorption. Dose: 50g orally. It is also used in the charcoal - haenioperfusion system to promote elimination from the circulation of sonic already absorbed poisons. Charcoal has also been used as impregnated dressings to deodorize foul smelling wounds and ulcers,
chenodeoxycholic acid A bile acid
derivative that has it solvent action on cholesterol-containing gallstones, and it is useful when surgical removal of the stones is contraindicated.
Dose: I g once daily, but prolonged treatment is necessary. Side-effects are diarrhoea and pruritus, and ursodcoxycholic acid, which has fewer side-effects, is often preferred. Chenodeoxycholic acid is not suitable for the dissolution of radio-opaque gallstones. (Chendol; Chenofalk).
chloral hydrate A water-soluble hypnotic with a rapid action that is useful in the treatment of insomnia in children and the elderly.
Dose:    g. It must be given well-diluted to reduce the gastric irritant side-effects, and is contraindicated in gastritis, and severe renal, hepatic and cardiac disease. (Notre). Chloral betaine (Well-dorm) is a less irritant alternative. See page 152 and Table 22.
chlorambucil An orally active cytotoxic drug used mainly in the treatment of lymphomas and chronic lymphocytic leukaemia.
Dose: 100-200 pgfkg daily for 4-8 weeks. It k sometimes used as an immunosuppressant in the treatment of rheumatoid arthritis in doses of 2.5-7.5 mg daily. Chloranibucil is generally well tolerated, [)of [)one marrow depression may occur, and haematological control during treatment is essential. (Leukeran). See page 122 and Table 8.
chloramphenicol A wide-range, orally active antibiotic but now used only in life-threatening infections where other drugs arc unsuitable.
Dose: 2g daily orally, but in severe infections, -So niglkg daily by i.v. injection. Care is necessary when giving chloramphenicolo infants as it may cause so-called ‘grey syndrome’. Side-effects include nausea, neuritis and aplastic anaemia. Chloromycetin is also used locally in skin, eye and ear infections. (Chloromycetin; Kcinicetine).
chlordiazepoxide A benzodiazepinc used mainly in [tic short-term treatment of anxiety and alcoholism.
Dose: 30 mg daily, increased in severe anxiety up to 100 mg daily, with half closes fix elderly patients. Withdrawal of treatment should be gradual to avoid rebound effects. Side-effects include dizziness, drowsiness and ataxia. Prolonged use carries the risk of dependence. (Librium).

chlorhexidine An antiseptic of high potency and a wide range of activity, although it is ineffective against spores and viruses. For preoperative skin preparation, a 0.5% solution in alcohol is often used; an aqueous solution (0.05%) is for general topical application. Chlorhexidine is also used as a  solution for bladder irrigation. A general purpose cream and an obstetric cream are also available. Solutions of chlorhexidine may become contaminated with Pseudomonas, and all aqueous solutions should he sterilized. (1-libitane).
irreversible retinal damage. Other side-effects are gastrointestinal disturbances, rash and prutiros. (Axioclor,). Swe page 16.3.
chlorothiazide The first of the thiazide diuretics, now largely replaced by bendrofluazide and similar drugs. Dose: 1 -2 g daily in oedematous states; 0.i-1 g daily in hypertension. Potassium supplements may be necessary with extended treatment. (Saltiric). See page 148 and Table 21.
29
chlormethiazole A sedative with anticonvul’ant properties.
Dose: in severe insomnia in the elderly, 200-400nigorally; in alcohol withdrawal conditions, 400-800 mg initially, reduced and withdrawn over a 9-day period. It may also be given by i.v. infusion as a 0.8% solution. Chlonnethiazole has also been given by injection in status epilepticus and the toxaemia of pregnancy in doses according to need and response. Side-effects are sneezing, gastrointestinal disturbances and headache. (Heminevrit) See page 136 and Table Ii.
chloroform Once widely used as a general anaesthetic, but now obsolete. Used as chloroform -water in mixtures as a preservative and flavouring agent, and for its carminative effects.
chloroquine An antimalarial drug used for both prophylaxis and treatment of benign and malignant tertian malaria. It should be noted that chloroquine- resistant strains of Plasmodiunifialciparurn are becoming increasingly common, and a return to treatment with quinine may be necessary. Dose: adult prophylaxis, 300nig once a week; (Or treatment of an attack of malaria, oWnig initially followed by 300mg daily for 2-3 days. Seriously ill or vomiting patients should be given 2(XI-300 ing by Lin. or slow i.v. injection, repeated once ifncccssary L)cfi)rc oral treatment can be tolerated. Other dosage schemes are also in use, and for details reference should be made to standard works on the treatment of malaria. It has also been used in hepatic anioebiasis, but nietronidazole is now often preferred. Chloroquinc also has an action in rheumatoid inflammatory conditions similar to that of penicillamine, dose: 150 mg daily after food. Such use requires care, as extended therapy is necessary, and the drug may cause corneal opacity and
chloroxylenol A general purpose antiseptic present in some popular products. Of no value against Pseudornonas. aeruginosa or Proteus.
chlorpheniramine An antihistamine with the action, uses and side-effects of the group, including drowsiness.
Dose: 16-24 mg daily: 10-20 mg by Lin. or .c. injection as required. (Piriton). See page 110 and Table 2.
chlorpromazine A powerful tranquillizer or antipsycholic agent with a wide range of activity on the central nervous system. It is widely used in the treatment of schizophrenia and other psychoses, in agitation and tension, and the management of refractory patients. It is also effective as an antienietic in terminal illness; in the short-term treatment of severe anxiety; and for the control of intractable hiccup.
Dose: initially 75 mg orally daily, slowly increased as required. In psychotic states, Lip to I g daily. Single doses of 25-50 mg may be given by deep imi. injection in acute conditions. Suppositories of 100 mg are also available. Side-effects include extrapyramidal and anticholinergic symptoms, drowsiness, hypotension, weight gain, rash, jaundice and haemolytic anaemia. prolonged use may cause pigmentation of the skin and eyes. Care is necessary in hepatic and renal dysfunction. Skin sensitization may occur after Contact With solutions of chlorpromazine. Margactil). See page 168 and’I'able 30.
chlorpropamide A long-acting hypoglycaemic agent of the sulphonylurea type. It is effective only if some insulin-secreting cells are still functional. It is used mainly in mild diabetes mellitus occurring in middle-aged patients not responding to dietary control. Its long action makes it unsuitable for elderly diabetics.

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.

Diet to Protect against Asthma
There is growing evidence that several aspects of the modern Western diet make asthma more likely to develop. Parts of this evidence are very convincing, while other findings are less conclusive as yet. Some people might argue that, until all the facts about diet and asthma are firmly established, no dietary changes should be recommended. However, all the dietary changes that might protect against asthma are also very valuable for general health.
This diet is potentially useful for:
0Atopic families who wish to reduce the chance of their chil- dren developing asthma. Other preventive measures, such as allergen avoidance and exercise (see Chapter 8), are obviously important as well.
•    Anyone who already suffers from asthma – with this diet, their symptoms may diminish.
The main elements of the anti-asthma diet are:
•    A high intake of fresh fruit. Researchers in Britain and the Netherlands have shown that people who eat more fruit have better lung function, and are less likely to develop asthma or bronchitis. Apples have a particularly good effect on the airways, according to one recent study. Many other studies show a link between Vitamin C – the major vitamin in fruit – and asthma prevention. This makes sense because Vitamin C is an antioxidant which inactivates the pro-inflammatory substances (called oxidants) that are found in cigarette smoke and other polluted air. In addition to Vitamin C, many fruits contain beta-carotene (see below) – mangoes and apricots are the richest sources.
•    Regular helpings of carrots, which contain the orange pigment beta-carotene. This is another antioxidant that can help prevent inflammation in the airways. It should be obtained from food, not supplements (see p. 207).
•    A high intake of fresh green vegetables, especially broccoli, spring greens, dark green cabbage, peas, parsley and courgettes. One Australian study has shown that children who eat fewer vegetables are more likely to wheeze. The benefits of vegetables may be partly due to the fact that they contain beta-carotene and (if eaten raw or only lightly cooked) Vitamin C. Dark green vegetables are also a good source of magnesium, and researchers find that people with a higher magnesium intake have healthier airways. Magnesium is believed to protect against asthma by helping the muscles of the airways to relax.
•    Plenty of tomatoes and tomato products, such as tomato juice, tomato sauce, ketchup and paste. The special protective effect of tomatoes is not entirely explained by their Vitamin C or beta-carotene content – another antioxidant, called lycopene, may be the crucial ingredient here. Good news for fast-food fans – the benefits of tomato paste are even seen among pizza eaters who are significantly less vulnerable to asthma.
•    Daily intake of sunflower seeds, or sunflower oil and margarine. These are by far the best natural source of Vitamin E, another antioxidant (see left) which helps to reduce the risk of becoming asthmatic. Vitamin E taken in supplements seems to have much less beneficial effect than natural Vitamin E from food.
•    A good intake of the minerals zinc, manganese and selenium, as well as magnesium (see p. 206). Shortage of any of these minerals may be linked with asthma. It is important not to eat too much wheat bran or unyeasted wholemeal bread, especially with main meals, as these block the absorption of several minerals.
Good sources of zinc include meat, shrimps, clams and oysters, with smaller amounts in cheese and egg yolks. Nuts, lentils and beans are fairly good sources of zinc, while soya protein blocks its absorption.
As well as being found in dark green vegetables, magnesium is plentiful in sardines, peanuts, hazelnuts, walnuts and lentils. Other fish, lean meat, milk, cheese and bananas contain smaller amounts.
Manganese is found in eggs and milk, and though the amounts are small, these are good sources because the mineral in them can be absorbed easily. While green leafy vegetables, whole grains and tea apparently contain more manganese – and are frequently recommended as a source of this mineral – in fact very little can be absorbed from those foods. Lentils are a moderately good source of manganese.
Selenium is most plentiful in fish and meat. It may be scarce in home-grown plant foods in areas of the world (notably Finland and parts of New Zealand) where selenium is lacking in the soil.
•    A limited intake of meat, especially red meat, plus a com-
-    plete avoidance of kidney, liver and other offal meats. An entirely vegetarian diet incurs a risk of mineral deficiencies however (see above). On balance, it is probably best to eat meat once a week or less.
•    A low intake of salt. Researchers in Kenya found that children eating a high salt diet (which equals the average salt intake in Britain and other parts of the developed world) were at greater risk of becoming asthmatic. For existing asthmatics, increasing the amount of salt eaten can make asthma worse, while reducing salt can lessen symptoms. Male asthmatics seem to be more vulnerable than females. Salt probably affects the muscles of the airways, making them more likely to contract.
The role of supplements
You should try to get all the nutrients you need from food rather than supplements. However, there are times when a supplement can be useful. Any asthmatic who has to cope with the effects of high air pollution, especially ozone and sulphur dioxide (see pp. 130-31), may find a supplement of Vitamin C beneficial. However, you should avoid very high doses of Vitamin C (e.g. I g/day) as they can cause disturbed sleep. Use natural sources for Vitamin E (see p. 206) if you can, but taking a supplement is better than nothing.
Vegans should think about taking a multi-mineral supplement, given the difficulties of ensuring an adequate intake of zinc, manganese and selenium from vegetable food (see left). Vegetarians may also benefit from a mineral supplement.
Some supplements, in certain circumstances, can do more harm than good. Omega-3 oils (also called w-3 oils, concentrated fish oils, or EPA and DHA) may make asthma worse for some people (see box on p. 221). Beta-carotene (sold alone and as part of mixed antioxidant supplements) may, according to some studies, promote cancer at the high doses used in many supplements. It should only be obtained from food.
Foods and drinks that bring on asthma attacks
The anti-asthma diet tackles the inflammation of the airways and the underlying tendency of the airway muscles to go into spasm – in other words, it is concerned with the long-term treatment or prevention of asthma. In addition, you should obviously avoid any foods which aggravate asthma in the short term. Various foods and drinks can bring on an asthma attack:
•    Foods and drinks containing sulphur-based preservatives tend to give off the irritant gas sulphur dioxide while being chewed or swallowed. Some asthmatics are more sensitive to sulphur dioxide than others. The foods that most commonly cause problems are dried apricots and other dried fruit (except those labelled ‘unsulphured’), shellfish, french fries, ready-made salads and fruit salads. Sulphur-based preservatives are used widely in the catering industry. On packaged food, look for ’sulphite’ and’metabisulphil or E numbers 220-227. Soft drinks, wine, beer and cider almost always contain sulphur-based preservatives.
•    Foods that cause heartburn (GER – see p.38) can aggravate asthma for some people.
•    Alcoholic drinks may make the airways contract for some asthmatics (see box on p. 160).
•    Some asthmatics need to avoid foods containing histamine (see box on p. 67).
•    A few asthmatics respond badly to the smell of food cooking. The most severely affected can suffer an asthma attack from anyfood aroma. Cromog lycate -type drugs (see p. 148) or anti -choli nerg ics (see p. 156) may block this reaction.
Needless to say, if you have a sensitivity reaction to any food listed for the anti-asthma diet you should not eat this food.

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.

A blocked or runny nose in Allergy
THAT LASTS ALL YEAR
`Everyone has heard of hayfever, but it’s news to most people that you can have this sort of problem all year round,’ complains Elizabeth. ‘Before we got the treatment sorted out, Benny was “the kid with the constant cold”, and I did notice other mothers looking less than enchanted at the prospect of his coming over to play.’
Benny suffers from allergic reactions to house-dust mites and cats which cause hayfever-style symptoms (26) all year round. This condition doesn’t even have a common name – the medical one is perennial allergic rhinitis – yet it is one of the most common allergic diseases.
Any airborne allergen that is found in the air all year round can cause perennial allergic rhinitis:
• House-dust mite is the number one suspect in most parts of the world. Particles from other insects, such as midges and mosquitoes outdoors, and cockroaches, house flies, bloodworms (used for fish food) or carpet beetles indoors, can also cause nasal allergies.
• Mould spores can be the problem: they are found both indoors and out.
• In some regions, certain types of pollen are airborne all year round (27).
• All pets other than fish produce allergenic particles (even snakes).
• Allergens encountered at work (133) can also produce symptoms in the nose. This is a warning sign gn you should not ignore – it often means that occupational asthma is on its way (132).
Occasionally, the offending substance is being eaten not inhaled. This is less common, so you should investigate inhaled allergens first, before trying an elimination diet (29).
Skin-prick tests (91) will help to identify any airborne allergens that are responsible, but where food is the culprit, skin-prick tests are often negative (69)
Triad and NARES
Diagnosis of perennial allergic rhinitis is complicated by the fact that there are two other conditions – called triad and NARES – which produce similar symptoms and involve the immune system but are not, strictly speaking, allergies.
Triad is so called because it involves three distinct symptoms:
• perennial rhinitis
• polyps in the nose – little fleshy growths that can kill your sense of smell
• asthma.
People with triad tend to collect all three symptoms gradually, in no fixed order, over a period of years or even decades. Many are sensitive to aspirin and related drugs, and almost everyone with triad develops this sensitivity eventually.
Aspirin sensitivity can come on very suddenly and produces a reaction akin to anaphylaxis (101). This can be fatal, so it is probably best to avoid all aspirin-like drugs if you have triad, even though you have not reacted to aspirin in the past Aspirin-like drugs are found in painkillers, arthritis drugs and cold remedies – check with a pharmacist before you buy (151).
If you have asthma, think twice about operations on the nose to remove polyps – they can make the asthma much worse.
The initial letters of Non-Allergic Rhinitis with Eosinophilia have been stretched a bit to get NARES. (This is a medical joke –the Latin word Hares means nostrils.) The problem is caused by eosinophils (19), which flock into the nose and cause severe inflammation. Some people with NARES go on to develop triad.
Collateral damage
Having the nose swamped with mucus can lead to knock-on problems in the ears, sinuses and airways.
If the tube that leads from the ear to the nose (the Eustachian tube) becomes blocked, then fluid cannot drain away from the middle ear. This is called secretory otitis media, or glue ear - it dulls the hearing and causes an unpleasant ‘popping’ sensation. The ears may also feel blocked and itchy, but if children have had this problem since they were tiny they may not complain because they assume that’s just the way ears are supposed to feel. Deafness is often the first sign anyone notices.
Sinusitis is another possible complication, because fluid from the sinuses should also drain into the nasal cavity. With the ouflow blocked, mucus builds up in the sinuses and can become infected by bacteria (30).
Post-nasal drip can also occur with perennial allergic rhinitis. The over-abundant mucus runs down the back of the nose, into the throat and then the airways. This produces a persistent phlegmy cough, which may occasionally be mistaken for asthma.
When the rhinitis is treated effectively, all these problems should sort themselves out, although additional treatment is usually necessary in the case of persistent sinusitis (33).
Treatment
Where an allergen such as house-dust mite or mould spores has been identified as the source of the problem, eradicating it from your house (see Chapter 4) will make a huge difference, and may avoid the need for drugs. If the allergen is unavoidable, immunotherapy (see pp. 164-8) or some alternative form of desensitisation (see pp. 210-13) could be very helpful.
Where drugs are needed, nose drops are best. They get the drugs right to the target so doses are minimal, which means very few side effects. The drugs used are:
• cromoglycate to prevent the allergic reaction before it starts (148)
• antihistamines to block the allergic reaction before it produces inflammation (138)
• steroids to calm down inflammation (144). Steroid nose drops are also useful for NARES and triad. If you are taking steroid drops continuously, your doctor should check the membranes inside your nose every six months. Make sure you put the drops in correctly, especially if you have polyps (144).
If you suffer stinging, burning or dryness, it might be due to preservatives in the drops, not the drug itself (see box on p. 33), so talk to your doctor about a different formulation.
Don’t use over-the-counter decongestant drops: they do nothing to treat the allergy or inflammation, and are little more than a ‘chemical crowbar’ to open up the nose. Your nose gets addicted to them in a few days, and when you stop using them you get ‘rebound congestion’ - absolute and total blockage. It does wear off eventually, but is unpleasant meanwhile. If you are suffering this problem at this very moment, don’t put more decongestant drops in - your nose needs to go ‘cold turkey’ to recover, not have its addiction fed!
If none of the anti-allergy drugs work, but decongestant drops do, then you probably have a non-allergic disease called vasomotor rhinitis. The symptoms are very similar to allergic rhinitis, but without the sneezing and itching. See your doctor again, because there is an effective treatment that uses anticholinergic drugs (see box on p. 156). Acupuncture (see below) can also be helpful.
An elimination diet (194) will diagnose any food reactions. It works wonders for some people with severe and unexplained perennial rhinitis, Including people with such a flood of mucus that they can scarcely work or live normally. You should certainly give this diagnostic diet a try if there are clues that suggest food is the culprit (69) or if no airborne allergen can be identified. Yeast - found in bread, beer and B-vitamin tablets -is quite often the culprit in rhinitis, but it could be any food.
Acupuncture is worth trying, to reduce the blockage in the nose and stem the flow of mucus, because the autonomic nervous system (see box on p. 235) plays some part in the symptoms of allergic rhinitis (and is the sole cause of the symptoms for those with vasomotor rhinitis). For those with severe sinusitis, osteopathy can be good for draining mucus from the sinuses.
Very occasionally, psychological or emotional reactions play a part in perennial allergic rhinitis, with symptoms getting significantly worse during stressful events. One possible manifestation of this is post-coital rhinitis, where sex brings on rhinitis (and sometimes asthma as well). In such cases, psychotherapy should be considered. (But check you are not just allergic to the dust mites in your bed first…)
A nose by any other name…
Rhinitis means inflammation (-itis) of the nose (rhin-). The same Greek word gives us rhinoceros - ‘nose-horn’.

Hayfever in Allergy

Foxtall grasses release their pollen - a potential source of hayfever symptoms.
`I gradually recognised that it was not an ordinary cold and that the symptoms were much worse on the

golf course or even during a nice day rowing on Loch Lomond.’ Dr John Morrison Smith, then a medical

student, began suffering from hayfever in the late 1930s. ‘At first I did not know what I had, and

neither did any other doctor I encountered in the next two or three years…’
All the classical allergic diseases (see box on p. 11) seem to be increasing, but none has exploded

quite so dramatically as hayfever. The physicians of Ancient Greece described asthma and food allergy,

and the Romans recorded allergy to horses, but there were no reports of hayfever. The only account –

and it is a doubtful one – comes from Persia in AD 925. Two hundred years ago, hayfever was unknown –

and careful research by medical historians has shown that this was not a case of it simply being

ignored, or misinterpreted as a cold.
The first case was reported in 1819, but even in the 1930s it was so rare that a succession of Scottish

doctors and medical students were baffled by Dr Morrison Smith’s symptoms. Today everyone knows what

hayfever is, since huge numbers of people sneeze and snuffle their way through the pollen season. There

are no certain explanations for this meteoric rise, but greater hygiene (21) may be an important

factor.
Symptoms of hayfever
The common symptoms of hayfever are well known:
• itchiness of the nose, mouth, throat and eyes – often the first sign
• a streaming and/or blocked nose
• frequent sneezing
• red, watery eyes (very rarely, hayfever affects the eyes only, with no symptoms in the nose).
Less commonly, there may be:
• dryness of the throat if the nasal blockage results in constant breathing through the mouth
• no sense of smell due to a blocked nose (but nasal polyps can also cause this – 30)
• a feverish sweaty feeling (but the body temperature is usually normal)
• swelling and inflammation of the eyelids, sometimes leading to blistering and ulceration: there

is a risk of blindness if this is not treated promptly
• recurrent sinusitis (30)
• earache, itching or a stuffy feeling in the ears, or ‘glue ear’ (29)
Some sufferers also experience:
• Oral Allergy Syndrome (an itchy tingling mouth) from certain fruits, nuts and vegetables (see

box on p. 63)
• a skin rash from pollen falling on the skin, direct contact with the leaves of the offending

plants, or with droplets of moisture from them – as when mowing a lawn or using a strimmer. If the skin

is cut or grazed, anaphylaxis can (rarely) result from direct contact with the plant (see pp. 58-9).
Even more rarely there can be:
• stomach upsets or even colitis (inflammation of the bowel) possibly due to pollen swallowed

with food or in the saliva
• irritation in the vagina
• migraine
• kidney inflammation (nephritis), leading to puffiness of the face and hands, and possibly other

symptoms
• joint pains.
The last two are probably caused by pollen allergens bound to their antibodies and carried in the blood

(13).
Diagnosis
The standard diagnostic tool here is the skin-prick test (see lo, 91). In diagnosing hayfever there are

three separate questions:
1 Is it actually hayfever?
2 Which pollen or pollens are responsible?
3 Are allergens other than pollen also involved?
Don’t be surprised if none of these questions is asked. In most countries, if you have hayfever-like

symptoms during the pollen season (i.e. when most hayfever sufferers have symptoms), the doctor will

conclude that you have hayfever - and that will be the end of that.
If hayfever seems plausible to you, and you respond to drug treatment, or manage well on pollen

avoidance (126), then -here is probably no reason to go further. Should you want a more thorough

investigation, you will need to be persistent. These are good reasons for requesting a full diagnosis:
• Your symptoms are worse in the pollen season, but they never really go away, suggesting that

you may be allergic to year-round allergens, such as house-dust mite or moulds, as well. It is worth

knowing which ones, so that you can avoid them. If you live in an area that is always warm (such as

California or Southern Australia) it may be that your culprit pollen is in the air all year round -

even so, knowing which pollen it is can help with avoidance. Around the Mediterranean, the pollen from

cypresses can keep hayfever going through the winter (or cause symptoms in winter only).
• Your symptoms are sometimes worse when they should be better, and vice versa. If you are

consistently worse indoors with the windows closed this could indicate that a seasonal indoor allergen

is the culprit - mould spores or cockroach perhaps (cockroach is often seasonal in regions with cold

winters - 118).
• Your symptoms begin before the pollen season begins, or go on long afterwards. Or the severity

of your symptoms does not match the daily pollen count for your suspect pollen. In Britain, the mould

Cladosporium herbarum produces spores in June, roughly coinciding with the grass-pollen season. Allergy

to this mould can easily be mistaken for grass-pollen allergy. You would need skin-prick tests for both

Cladosporium and grasses.
• You are much worse near home than elsewhere. It could just be a garden plant or tree. As one

California resident observed, ‘The worst offender was an olive tree on our front lawn. It’s been

removed.’
• You want to plan holidays free from the culprit pollen.
Moving house - especially to a region with different vegetation
- can be a spur to finding out exactly what your allergens are. If you are going for a full diagnosis

make sure it is done correctly. Don’t accept testing with ‘mixed tree and shrub pollens’ for example,

or ‘weed pollens’. The result tells you very little. Ask for tests with specific pollens.
Treatment
Too many people allow hayfever to spoil the summer months because they are anxious about taking drugs,

or feel that it is nobler to suffer. This book is not in any way complacent about the dangers from

drugs (see Chapter 5), but when it comes to hayfever there really is very little cause for concern. The

risks with drugs used for hayfever are absolutely minimal, and it is such a waste to miss out on the

best time of year.
Most hayfever responds very well to treatment with antihistamines (138). If they make you sleepy,

persist for a while, because this side effect often wears off - or ask for one of the new non-sedating

forms. The sleepiness is annoying, but it is only a minor side effect, and not an indication of the

drug causing any serious harm.
Cromoglycate drops (for the eyes or nose) do not work for everyone, but if they work for you, go for

them. These are absolutely the safest of the anti-allergy drugs. Steroid drops for the nose (144) are

also recommended. The dose of steroid involved is small, and very little gets into the bloodstream, so

there is no risk of serious side effects. If you suffer stinging, burning or dryness, it might be due

to preservatives in the drops, not the drug itself (see box on p. 33). Steroid drops for the eyes

should be used cautiously (144). Don’t use over-the-counter decongestant drops for more than three days

(29).
Immunotherapy is standard treatment for hayfever in many countries, but in Britain you will have a

struggle to get it (see pp. 164-8). Some hayfever sufferers feel they do well with homeopathy (215) or

acupuncture (214).
Pollen asthma
Some people with hayfever also have pollen asthma. Their asthma is worse in the pollen season but it

usually persists all year round (either because there are other allergens or irritants involved, or

just because the inflammation of the airways is self-perpetuating) whereas hayfever itself clears up.

Treating the hayfever fully with antihistamines helps considerably with the asthma symptoms.

 

In medical terms, this article covers a lot of ground.
First there are the classical allergic diseases
 such as hayfever and immediate food allergy, which are caused by the allergy

antibody, IgE .
Then there is non-IgE immune sensitivity, a category which includes a number of quite different

diseases, caused in a great variety of ways. They also vary in severity - there are serious lifelong

problems such as coeliac disease and minor short-lived problems such as contact dermatitis from garden

plants.
Finally the chapter looks at diseases where the immune system seems not to be involved, or

plays only a minor role: the intolerance reactions to food and synthetic chemicals. These are diverse

and rather mysterious in origin. They would not be described as ‘allergies’ by most doctors, though

they often are by complementary therapists (6).
These categories are not nearly as neat and tidy as they might sound. Some problems refuse to fit

anywhere, such as atopic eczema caused by food. A percentage of children with this problem have IgE to

the food concerned, while others do not - so where does it belong?
If you were expecting an answer to that question, you will be disappointed. Nor, quite often, are there

any certain and honest answers to questions such as ‘Has my baby really got asthma?’ or ‘Can you be

sure it’s irritable bowel syndrome?’ There are no answers to
such questions because most diseases do not exist in neat compartments, and the words we use to

describe them really denote rather abstract concepts.
This does not mean that the terms used to describe diseases are invalid - doctors and medical

researchers invent them to try to make sense of a complex, confusing and largely foggy reality. They

also argue over them, split them, unite them and redefine them. There is a constant desire to get the

medical picture of that foggy reality more precise and accurate (although medical politics gets

involved too - 7 -which is unfortunate).
Over time, thanks to huge amounts of research effort, things gradually get clearer. You’ll no longer

hear a doctor talk about ‘rheumatism’ or ‘arthritis’, because it was long since realised that these

categories were useless - they included a number of diverse diseases. And while doctors might say ‘food

poisoning’ or ‘heart attack’ or ’skin cancer’ to a patient, they use much narrower and more precise

terms when talking among themselves, and when ordering tests or prescribing treatment. Each of these

categories has been split into several well-defined sub-categories.
Ideally, this process of splitting continues until each disease category has a set of well-defined

symptoms (this set is known as a syndrome), plus a few simple and definitive diagnostic tests. This

will probably depend on the cause of the disease (the mechanism in medical jargon) being clearly

understood. Once the mechanism is clear, then a disease category is a truly satisfactory tool for

diagnosis and treatment.
Of the disease categories mentioned in this book only a few, such as coeliac disease and hayfever, have

reached that happy state. The majority are still somewhat arbitrary and debatable.
Some disease terms describe a set of symptoms with no clear underlying cause, for example, ‘irritable

bowel syndrome’. Others describe a well-defined response by the body, that can be caused in many

different ways - an endpoint that can be reached by various routes. This is true of ‘asthma’ or

‘urticaria’.
A third type describes a much less well-defined cluster of symptoms. Idiopathic food intolerance,

chemical intolerance and yeast overgrowth all come into this category. A few doctors don’t even see

some of these clusters as real diseases because the symptoms involved are so vague and so widely

encountered. Some of the arguments used to dismiss idiopathic food intolerance are dissected on pp.

74-7. A key point made against these diseases is that the symptoms they produce are non-specific -

common symptoms such as headache, fatigue and diarrhoea, which can arise in a great variety of ways.

Ever since Pasteur and the germ theory, medicine has been based on the idea of each disease having

specific symptoms and specific causes, and it has roared ahead on the basis of this assumption. This is

the prevailing paradigm of modern medicine, and like all
paradigms it blinds people to facts that don’t fit. Evidence is accumulating that there are diseases

which have multiple, non-specific and variable symptoms. Chronic Fatigue Syndrome (CFS - see box on p.

85) is one of these, and its recent transformation from a doubtful diagnosis to a reputable disease

recognised by conventional medicine suggests that the paradigm might be starting to crack.
To sum up, the business of identifying and naming diseases is a complex and uncertain process, in which

the concept of most diseases is only ever that - a concept, subject to change and refinement. This does

not make it worthless - quite the opposite. These concepts are the best we can do at the present time,

and accurate diagnosis is the key to getting the best treatment available now.
As regards both diagnosis and treatment, this book covers a very wide spectrum of medical opinion, from

the entirely orthodox to the frankly whacky. I have tried to give an objective view of these different

opinions and approaches, using the evidence currently available, in the hope that it will help readers

to improve their health while wasting as little as possible of their time or money. In using this

information, you should always try to work closely with your doctor (96), respecting the depth and

breadth of knowledge that conventional medicine has to offer.

 

`When I first arrived in Charlottesville in 1982, the senior allergist said “I’ve got to warn you that here in Virginia we have patients who have very severe fungal infection of their feet, and they also have urticaria. If you treat their feet, their urticaria gets better.”‘ Professor Tom Platts-Mills of the University of Virginia in Charlottesville is recalling how his innovative studies of fungal infections and allergy began. That surprising observation about athlete’s foot (a fungal infection) and urticaria (nettle rash) was made by his predecessor, Professor John Guerrant,
‘I followed his advice,’ Platts-Mills continues, ‘and found he was right. Then I started noticing asthmatics in our allergy clinic who also had fungal infections of their feet. They were mostly men with severe adult-onset asthma. We gave them skin-prick tests with the fungus Trichophyton and these were positive – showing they had an allergic reaction to it. So we tried treating them with anti-fungal drugs and the asthma got much better.’
This discovery is not an isolated instance. Research over the last decade or so has revealed that allergic reactions to long-standing infections (chronic infection is the medical term) are far more common than anyone expected. Infections by fungi are frequent offenders.
An infection becomes chronic because, although the immune system tries to rout the infectious agent, it never succeeds. Making IgE may be part of that futile defensive effort. Once the immune system starts making IgE against the allergens produced by the infectious microbe, new symptoms may begin, or existing allergic symptoms may get much worse. The link between the infection and the allergy is far from obvious, however. Both the allergens and the IgE can be carried in the
Fungal infections
‘Fungus’ means everything from an edible mushroom or a huge bracket fungus to the specks of mould on stale bread or a shower curtain. Fungal infections are caused, not by mushroom-like fungi, but by inconspicuous mould-like forms, or by yeasts (which are single-celled fungi).
Once they are flourishing, some fungal infections may be seen as whitish or creamy-coloured patches. But at an earlier stage, the fungi are so small that they cannot be seen without a microscope. They spread as invisibly as bacteria or viruses.
Some infectious fungi can exist in two different forms – a mycelial form (long thin strands, as in a mould) or a yeast form (single cells).
bloodstream, so the symptoms may be somewhere else in the body, far away from the site of infection.
If the symptoms of the infection itself are relatively mild, they may not receive medical attention. Infection-plus-allergy often explains severe long-term allergic problems for which no cause could previously be found. This is the kind of case that gets labelled as ‘intrinsic’ or ‘endogenous’, because all the allergy tests have proved negative. Most patients in this category have had years of simply being treated with steroids (often at high doses) to suppress the symptoms.
Sometimes the infection-plus-allergy is part of a larger picture, with other allergens or irritants also contributing to the symptoms, but with no stunning improvements when they are avoided because the allergic stimulus from the infection remains.
The links between allergy and fungal infections – all those that have been discovered so far – are described below. In such cases, anti-fungal drugs, taken by mouth, usually in capsule form, could be of value. However, they must be taken for an adequate length of time, normally several months.
Bear in mind that, with the possible exception of chronic sinusitis, an allergic reaction to fungal infection is a relatively uncommon cause of symptoms. It is important that, with the help of your doctor, you start with the more likely suspects such as airborne or contact allergens. These are described in detail, for each allergic disease, in the relevant sections of Chapter 2.
Asthma
the common causes and usual treatment of asthma.
Trichophyton – the fungus that causes athlete’s foot – can provoke allergic reactions that contribute to asthma, as already described. This fungus may also infect other parts of the body. Trichophyton diseases have names that begin with tinea (athlete’s foot, for example, is tinea pedis). Other terms you may come across are intertrigo (an itchy rash which develops in skin folds) and onychomycosis (also called `ringworm of the nails’ or tinea unguinum). The research on the link with asthma was published in a respected medical journal, The Lancet, but has been widely ignored, so if you think you have this problem, you may have to be quite persistent with your doctor. Very thorough treatment with anti-fungal drugs (swallowed in capsule form) is required.
Chronic urticaria
many possible causes of chronic urticaria.
Trichophyton infections in any part of the body (see above) can provoke allergies, producing chronic urticarla. A great variety of other infections, including fungal, viral and chronic bacterial
infections, can be the root of the problem in chronic urticaria . However, this may not be an allergic reaction. It could be a direct effect of the infection, provoking the immune system in such a way that it triggers mast cells by itself, without IgE.
Chronic sinusitis
 the causes and treatment of chronic sinusitis.
Long-standing (chronic) sinusitis may be due to a fungal infection with a subsequent allergy. This is now called allergic fungal sinusitis. Some doctors believe that a sensitivity reaction to fungal infection (not necessarily an allergic reaction) could account for 96% of chronic sinusitis. However this is widely disputed .
Atopic eczema (atopic dermatitis)
the causes and treatment of atopic eczema.
The Trichophyton fungus can infect eczematous skin, though this is far less common than infection by Staphylococcus aureus (see below). Among patients infected by it, there can be an allergic reaction to Trichophyton which then makes the eczema worse.
There can also be an IgE reaction to a yeast, Pityrosporum ovale (also called Malassezia ovalis), in atopic eczema. This yeast is a commensal – i.e. a natural, and normally harmless, inhabitant of healthy skin. The inflammation of eczema makes the immune system far more tetchy so that it reacts allergically to this yeast, an innocent bystander which it normally disregards.
Candida  can also provoke an allergic reaction in eczematous skin. This is a more complex story, because while Candida is a commensal in the gut, it does not normally live on the skin. However, it may flourish in the disturbed skin of eczema patients.
Those with atopic eczema may also develop an allergic reaction to toxins from Staphylococcus aureus, a bacterium that often infects skin which is inflamed by eczema and damaged by scratching. Antibiotics are needed to treat the infection .
Seborrheic dermatitis
Not so long ago, this disease – which causes a red, scaly rash on the forehead, nose and cheeks, and sometimes on the chest –was labelled ’cause unknown’. Now most doctors believe that the yeast Pityrosporum ovale could well have a role in causing it. This yeast is part of the normal skin flora (see above), but it is found in greater numbers on the skin of seborrheic dermatitis patients. As well as overgrowth of the yeast, there is an immune reaction against it, usually involving the antibody known as IgG, rather than Fungi in the lungs
One form of infection-plus-allergy has been well recognised for many years - allergic bronchopulmonary aspergillosis, often shortened to aspergillosis.
The problem starts with the fungus Aspergillus fumigates, a ubiquitous mould that is found in special abundance in damp straw, compost heaps, bird cages and any decomposing material. Its spores are everywhere, and most immune systems quickly defeat them, but in some people, especially those with asthma, the spores begin to grow in the lungs. The fungus is found in the lung mucus, but does not actually invade the lungs. However, an allergic reation then occurs to the fungus.
This disease often goes together with asthma, or can be mistaken for asthma. There are three clues that point to aspergillosis:
• rubbery plugs of phlegm, either golden-
brown or green in colour
• fever whenever the asthma is severe
• worsening symptoms despite treatment.
Allergic bronchopulmonary aspergillosis is treated with steroids to control the allergic reaction, and physiotherapy to clear the mucus from the lungs.
Anti-fungal drugs have not proved very effective in the past. There are some newer anti-fungal drugs that may well be more useful, such as itraconazole and terbinafine. These are not widely used for aspergillosis at present, except in patients who also have cystic fibrosis or an immune deficiency. Because there has been no large-scale trial of these drugs, they are not usually given to people who simply have aspergillosis. However, they are sometimes prescribed for people who are unable to take steroids, or are not responding to steroid treatment. Anti-fungal drugs may become more widely used in the next few years, so it is worth discussing the possibility of this treatment with your doctor.
the allergy antibody IgE. Only about 12% of people who suffer from seborrheic dermatitis make IgE against the yeast.
One problem with seborrheic dermatitis is that, while it may improve with anti-fungal treatment, it usually comes back when the treatment stops. Doctors have therefore been looking for ways of keeping seborrheic dermatitis at bay after a successful course of anti-fungal treatment. One method that seems to work is to use a good anti-dandruff shampoo, in place of soap, to wash your skin once a week.
A medical earthquake
The recent discoveries about infection-plus-allergy have not posed any serious challenge to conventional thinking about allergy, because a disease of just this kind - aspergillosis (see box at left) - was already well known. A far more fundamental shake-up of traditional ideas about allergy and sensitivity has been necessitated by new research into atopic eczema. It is little short of an earthquake in the basic concepts of allergy and sensitivity.
To understand the extent of this earthquake, you need to know about the time-honoured system for classifying hypersensitivity reactions, which recognises four distinct types:
• Type I hypersensitivity — the IgE-mediated allergies  such as hayfever.
• Type II hypersensitivity - irrelevant to allergy, these antibody reactions mainly occur after transplant surgery, if the transplanted organ is rejected.
• Type III hypersensitivity - caused by a massive overload of antibodies and antigen in the blood. It is a feature of certain infections and autoimmune diseases, and can also occur in allergic reactions, though this is rare (13).
• Type IV hypersensitivity - the odd man out, because antibodies are not involved, or are not of central importance. Immune cells that can launch a direct attack are the movers and shakers here. These attacking-cells are sensitised for a particular antigen, such as dust mite or lanolin. Type IV hypersensitivity is a very slow reaction. Generally speaking, 48 hours pass, after an encounter with the offending substance, before the symptoms appear. The most common form of Type IV hypersensitivity is contact dermatitis (54).
Mystery has always surrounded atopic eczema. Although it crops up in the same atopic families that suffer from hayfever and asthma, and high levels of IgE in the bloodstream are typical of the disease, the actual role played by allergies in causing the symptoms is far from obvious.
The results of skin-prick tests - the standard test for an IgEmediated reaction - are puzzling. Patients tend to give a lot of positive results, many of which don’t mean much - the substances concerned do not provoke actual symptoms. On the other hand, skin-prick tests are often negative for substances that clearly do cause symptoms in challenge tests. Many children who regularly get eczema when they drink cow’s milk, for example, give a negative skin-prick test to milk. This conundrum has puzzled allergists for decades.
New discoveries about eczema do not entirely solve the puzzle, but they do go some way towards an answer, by revealing an immune response that cuts across the traditional categories. The most surprising fact is that even where skin-prick tests are positive and milk-specific IgE is involved in milk-induced eczema, this is not necessarily a standard IgE-mediated allergy.
While IgE antibodies may be involved, they are not necessarily teamed up with mast cells, their usual partners in crime (see box on p. 12). Instead, the IgE molecules are attached to special skin cells called Langerhans cells and dendritic cells. These have the role of picking up the antigen and showing or ‘presenting’ it to attacking-cells in the skin (a task called antigen presentation which is the ‘go’ signal that starts off all immune reactions).
The involvement of these attacking-cells, which are sensitised for a particular antigen, was a big surprise when first discovered. It makes this resemble a Type IV hypersensitivity reaction rather than a Type I.
IgE is not essential here, it seems — some patients do not have IgE for the substance that triggers their atopic eczema — but when Langerhans cells and dendritic cells are associated with IgE they do become far more zealous. This excitement is communicated to the attacking-cells, which mount a more powerful attack.
It looks as if what really matters in atopic eczema is the presence of antigen-specific attacking-cells in the skin, plus the heightened activity of the Langerhans cells and dendritic cells. If the individual has IgE for the antigen, it can play a part, but it is not essential.
In other words, this reaction cuts across two different categories of immune response — Type I and Type IV. (However, the kind of antigens that provoke the reaction are typical of IgEmediated allergy, rather than the kind of antigens that provoke contact dermatitis.) This has been exploited in a new and more sensitive set of diagnostic tests for food-induced atopic eczema (69).
Why atopic eczema is a feature of atopic families is the crucial question that remains unanswered. One factor may be that high levels of IgE in the bloodstream (not IgE for a particular allergen, but total IgE) make the whole immune system more excitable and prone to over-react. The next few years will no doubt solve this part of the puzzle too.
Peace-keepers or aggressors?
`It is bad enough having a child on an ultra-strict diet — Tim can’t have even a trace of cow’s milk or else he becomes violently ill. What makes it worse is when people — teachers, for example —ask what’s wrong. I take a deep breath and say “eosinophilic oesophagitis” then watch their eyes roll in disbelief.’
Tim’s disease is caused by a particular type of immune cell called an eosinophil. In the right circumstances, eosinophils can be valuable — like IgE and mast cells, they are geared to destroying parasitic worms . They produce some very toxic substances to kill these invaders, and it is the toxins that cause serious symptoms for Tim and others like him.
Any disease with ‘eosinophilic’ in the name involves vast numbers of eosinophils converging on some unfortunate part of the body. The stimulus that attracts them often remains unknown but once there, the toxins they generate cause inflammation (140) of a particularly violent kind.
It is only in recent years that doctors have begun to distinguish between patients such as Tim and children with classical food allergy, and to understand the cause of Tim’s symptoms. Several different forms of eosinophilic food sensitivity are now recognised (72). The exact relationship with IgE-mediated allergy remains a puzzle, because some sufferers make IgE to the culprit food but others do not.
That is not all — the eosinophil is finally coming out of the shadows and being recognised as an important agent in classical allergic diseases as well.
The fact that eosinophils appeared during the aftermath of an allergic reaction had long been known, but their role was misunderstood. What confused researchers was that eosinophils can break down histamine, the substance that kick-starts allergic symptoms. This ability gave eosinophils the appearance of peacekeeping troops, coming in at the close of battle to restore order. In fact, eosinophils are major aggressors — they do a whole lot of other things besides breaking down histamine, most of them pro-inflammatory. They can release toxins, just as they do in eosinophilic diseases, and they attract other inflammatory cells into the area. In short, eosinophils play a big part in keeping allergic reactions going once the initial burst of activity is over. This `Late Phase Reaction’ is enormously important .

 

how does allergy begin?
A mast cell, magnified about 10,000 times. The black granules contain histamine.
`At the beginning, I thought I just had a cold. I kept sneezing and coughing, and my nose was dripping. It got better at the weekend, and I thought — that’s good, it’s gone — but then on the Monday evening it started up again. The next thing I knew, I kept getting breathless. I’d been at the sawmill a month when it began. We were cutting planks of red cedar all day, and the dust was bad, it’s true. But I didn’t know that sawdust could cause you allergies. We were given dust masks, but they made you too hot. No one wore them. I found out later, from the doctor, that some men could work years at it before they got allergic to the dust, but with me it was just a month.’
Like many people with work-related allergy, Dan can actually pinpoint the time he became sensitised – when he began making IgE antibodies against the red cedar dust allergen. For allergies that are not caused by workplace allergens, this is rarely possible. The moment when symptoms begin may be obvious, but that is often long after sensitisation (making IgE to the allergen) first occurred. Long-term studies of children show that they may start giving positive skin-prick tests to pollens (a sign that they are making IgE to those pollens) while they are toddlers, but not develop hayfever until ten years later.
The basics of immunity
The immune system defends the body against infections and cancerous cells. One of its key jobs, before going on the offensive, is to recognise the difference between:
• self and non-self (e.g. the cells lining the lung, and bacteria trying to infect the lung)
• safe-non-self (e.g. a sandwich) and dangerous-non-self (e.g. Salmonella bacteria in the sandwich).
Through mis-regulation the immune system can cause:
• allergies (perceiving safe-non-self, such as pollen, as dangerous-non-self)
• autoimmune diseases (perceiving self as non-self).
The immune system consists of dozens of different kinds of cells (the immune cells) and a number of different antibodies – specialised ‘guided missiles’ (see box on p. 15) which are produced by certain immune cells.
There is also a huge array of messenger chemicals, which send general instructions (e.g. ‘calm down!’, ‘go for it!’ or’exterminate!’) from one type of cell to another.
Immune cells are self-contained units, many of them mobile and dispersed throughout the body. They travel around in the blood, and can move out of the blood vessels and into the surrounding tissues (skin, lung, nose, etc.).
These different components – immune cells, antibodies and messenger chemicals – interact in very complex ways. When an immune reaction occurs – i.e. the immune system recognises something, or mounts an attack on something – numerous different players are involved. All the reactions described in this book are very simplified versions of what actually happens.
Research shows that the first two years of life is the most vulnerable time as regards sensitisation to allergens. Very often, sensitisation occurs in the first few months, and sometimes even before birth.
Why is a young infant so easily sensitised? The answer lies not with the baby, but with the pregnant mother-to-be, whose immune system has to overrule its natural inclination to attack anything that is non-self. Potentially, a woman’s immune system could reject a foetus in just the same way that heart transplants are rejected. To prevent attacks on the foetus, the immune system is re-tuned during pregnancy, with one aspect of immunity – the part that’s most keen to attack a foreign body – being damped down.
This aspect of immunity is coordinated by cells known as T-helper-1 cells, or Th1 cells for short. To protect the foetus, these Th1 cells are asked to ease up during pregnancy. Meanwhile, since immune protection is still needed, their colleagues, called T-helper-2 cells or Th2 cells, become more active.
The classical allergic diseases
These four pages are concerned only with the classical allergic diseases, that is:
hayfever (an allergy to pollen)
perennial allergic rhinitis (a nasal allergy to a year-round allergen such as house-dust mite)
asthma where this includes an allergic reaction atopic eczema (42)
urticaria (nettle rash or hives) where this is allergic in origin, and the accompanying angioedema (swelling due to fluid escaping from tiny blood vessels into the surrounding area; it is sometimes called ‘water retention’)
anaphylaxis (a violent allergic reaction to food, insect stings, penicillin, latex, etc.)
food allergy (in most cases, an immediate and marked reaction to food, with symptoms in the mouth; there may also be anaphylaxis).
Running the immune system
T-helper cells are, in a way, mis-named, because they do not help at all – they just give orders.
These are the supervisors of the immune reactions, telling other immune cells either to lie low or to get busy. Where Th1 and Th2 cells differ is in the types of immune cells they send into action. Among those who get their go-ahead from Th1 cells are immune cells that attack directly, without producing antibodies – these are the ones that reject transplants and could, if given free rein, reject a foetus or retard its growth.
The Th2 cells, on the other hand, have among their preferred troops the immune cells that produce IgE antibodies – the allergy-causing antibodies. So one effect of protecting the foetus from rejection is to push the immune system towards a greater tendency to allergy.
This shift of emphasis occurs in the mother’s immune system, but it carries over into the immune system of the foetus because they are sharing the same blood supply, and the blood contains the messenger substances which fine-tune the immune system. Immediately after birth, the baby’s immune system is still following the same pattern, continuing to upregulate Th2 cells and downregulate Th1 cells. This is a crucial factor in setting the stage for allergic sensitisation.
Ideally, the world that the baby encounters just after birth should nudge the immune system in the opposite direction and get it operating in a non-allergic way. But the world in which we live is far from ideal in this regard.
For one thing, it is much too clean. As far as the immune system is concerned, ‘ideal’ would mean encountering quite a bit of dirt, such as garden soil, in the early stages of life. The soil contains harmless bacteria which do not cause any symptoms, but do tweak the immune system towards Th1 cells and away from Th2 cells. Bacterial products in household dust may do the same thing (21).
A long period of consuming nothing but breast milk would also suit the baby’s immune system rather better than being fed on cow’s milk formula or being suddenly weaned onto a number of highly allergenic foods, such as egg, wheat, soya (ubiquitous in The basic cause of classical allergy is an immune reaction involving mast cells and IgE antibodies.
Mast cells are plentiful in the lining of the nose, the airways, and the digestive tract. They have counterparts in the blood, called basophils.
Seen under the microscope, both mast cells and basophils look very granular inside. The granules are tiny storage compartments, containing stockpiles of messenger chemicals, notably histamine.
Histamine causes several different reactions:
• contraction of muscle around the airways. This reduces the diameter of the airway, producing an asthma attack.
• widening of blood vessels
• increased leakiness of the smallest blood vessels, allowing fluid and immune cells to escape into the surrounding area – for example, the skin or airway lining
• as a result of these two above effects, local swelling (called oedema or angioedema) and irritation – in the skin this is experienced as urticaria, or nettle rash, in the nose it causes blockage, itching and sneezing
• if sufficient histamine is released into the blood, a drastic fall in blood pressure, due to widespread opening of blood vessels, and leakage of fluid into the tissues; this occurs in anaphylaxis (58).
Histamine is released when mast cells are activated, a process called degranulation because the cells discharge their storage granules.
Mast cells release other substances at the same time, some of which attract more immune cells to the area, causing more inflammation. They help to produce a ‘Late Phase Reaction’ which occurs after the initial allergic reaction has died down, and lasts about 24 hours (13). Once activated, mast cells also start making messenger chemicals called leukotrienes which are highly inflammatory.
What causes a mast cell to degranulate? The answer is found on the surface of the cells, where the allergy antibody, IgE, sits. One end of the IgE molecule is bound to the mast cell, and the other end can bind to the allergen concerned. In someone allergic to egg, for example, egg allergen will bind, with great specificity, to egg-specific IgE antibody.
For the receptors to pass a message to the mast cell there have to be two IgE antibodies specific for the same allergen on the mast cell – and the allergen has to bind to both these IgE molecules, cross-linking them. This is the ‘go’ signal for the mast cell to degranulate.
processed foods), fish or peanuts, before it can handle them. Not taking antibiotics before two years of age would also help (although it might, of course, be very bad for the baby in other ways). Exactly why is not yet fully understood .
An ideal world for the immune system would also lack the by-products of cigarette smoking, whether in the blood of a pregnant woman or in the air that a baby breathes – both seem to promote the allergic tendency. In addition, the perfect world would lack central heating, fitted carpets, draught-proofing and thick upholstery. A house like this is heaven for house-dust mites but not for innocent young immune systems.
The problem with house-dust mites – apart from the fact that they breed like wildfire, and hole-up in mattresses, armchairs and soft toys – is that they produce a highly allergenic protein in their droppings. This protein interferes with the membranes of cells, making them less stable. It irritates various immune cells, including mast cells (see box at left), and can even make mast cells degranulate, as if there were a true allergic reaction happening.
Once mast cells have done this, they release messenger substances that arouse the immune system and make a genuine allergic reaction –beginning with the production of IgE to the dust-mite allergen – much more likely. In other words, dust-mite allergen is an agent provocateur, an aggressive substance that actually provokes the immune system into reacting allergically.
Until recently it was widely assumed that allergens were just inoffensive, passive substances which the immune system happened to take objection to, in a distinctly unreasonable way. The new discoveries about dust-mite allergen raise the question: could other allergens be more aggressive than previously thought? Certainly the peanut allergen, or other substances found in peanuts, seems to destabilise cell membranes, which may explain why this allergen so easily sensitises young children.
The role of genes
Faced with this non-ideal world, many children pull through without developing allergies, but others do not. This is where genes come in, making one child more susceptible to our allergy-promoting lifestyle and another child less so. Exactly how the genes make this difference is still not fully understood, but there are at least twenty genes involved , and it is clearly going to be a complex story. The overall effect of these genes is a greater tendency to make IgE, combined with mast cells and basophils  that are distinctly trigger-happy –much more eager to degranulate than in healthy individuals.
Given all the mayhem caused by mast cells and IgE, why does the body produce them at all? They cause a lot of damage to allergy sufferers and do little apparent good, at least for people in the Western world. The value of the mast-cell-IgE-reaction, for most of us, is historical – it wages war against large-bodied parasites such as tapeworms and schistosomes. (They are large by comparison with bacteria and viruses, and not easily tackled by other immune cells.) These unpleasant invaders have largely been eliminated in the developed world but are still rife in other countries. For millions of years such parasites were an inevitable part of human life, and this bit of our evolutionary past survives in our immune system.
The complexity of allergic reactions
`Each time the pollen season came around. I would start to get these pains, especially in my knees. I asked my doctor about it but she just looked at me rather oddly and said “take a paracetamol”. I couldn’t be sure it was linked to my hayfever, but the pains always came on just after the sneezing started. One year, it was all worse than usual, and I felt very tired too. My face was all puffy and I could feel that something was seriously amiss. That, as I now know, was because my kidneys were being affected. It was years before the doctor would refer me to an allergist, and I actually got an explanation for all this. I think for a long time my doctor thought I was making it up, or just imagining the pain in my knees.’
Karen suffers from a rare complication of hayfever involving an overload of pollen antigens and antibodies in the blood. Very large numbers of both are involved, and are bound to each other in dense tangled masses called immune complexes. Because these are carried around in the blood they are known as circulating immune complexes. They may be too large to be cleared quickly by the normal junk-munching systems that keep the blood clean.
Like a river choked with fallen leaves, which deposits some of the debris on its banks as it flows past, the blood inevitably
The other antibodies
Other than IgE, four main types of antibody exist – IgA, IgD, IgG and IgM. Although some of these antibodies help fight bacterial and viral diseases, they lack IgE’s ability to tackle certain large parasites. These other antibodies do not generally bind to mast cells, and therefore do not cause IgEstyle allergy. But they can be involved in various other sensitivity reactions – it is IgG antibodies that are active in coeliac disease for example, and IgA in dermatitis herpetiformis. And any kind of antibody can participate in circulating immune complexes, causing multiple symptoms (see below).
leaves behind some of the circulating immune complexes. They mostly become deposited in the tiny blood vessels called capillaries, particularly those in the skin, the kidneys and the joints. Inflammation (140) here can cause a range of symptoms.
This problem is known to doctors either as serum sickness or as Type III hypersensitivity. It is a well-known feature of several infections and of some autoimmune diseases.
Unfortunately, the potential for Type III hypersensitivity in allergies such as hayfever is much less well known among doctors, as Karen discovered. As well as affecting hayfever sufferers, Type III hypersensitivity can also be a complication of reactions to penicillin and certain other allergic reactions, such as insect-sting allergy.
When a reaction occurs to snake anti-venom – and it only occurs in an individual who has received snake anti-venom before – this too is Type III hypersensitivity. The snake anti-venom is cultured in horses, and the snake-bitten human who has received the snake anti-venom previously mounts a massive immune reaction to the horse proteins when snake anti-venom is injected for a second time. Large and numerous circulating immune complexes are formed, and although IgE is not involved, a very severe anaphylactoid reaction (see box on p. 59) follows.
Circulating immune complexes do not affect most allergy sufferers. But there are other immune responses that follow on from the initial allergic response in everyone with allergies –they are generally summed up as the ‘Late Phase Reaction’. This reaction starts 4-12 hours after the exposure to the allergen, and lasts about a day. It involves a number of different immune cells (including eosinophils – p. 19) and an even more varied array of messenger chemicals, making everything very complicated for medical researchers to investigate. When allergic symptoms become entrenched and difficult to treat, the Late Phase Reaction is usually implicated. But it has not been given much attention by doctors until recently, because the details are so complex and so poorly understood.