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Posts Tagged ‘Staphylococcus’

A-Z Principal Drugs (carbon dioxide - cephalosporins)

Wednesday, June 24th, 2009

carbon dioxide A colourless, non-inflamniable gas. It has a stimulating effect on the respiratory centre, and a mixture of 5% of carbon dioxide in oxygen is used for respiratory depression. Solid carbon dioxide is used to destroy warts, naevi, etc.
carbonic anhydrase inhibitors These drugs, represented by acetazolamide and dichlorphenamide, have been used as diuretics as they inhibit the reabsorption of sodium and bicarbonate in the kidneys. Their use has declined as more effective diuretics have become available. They also reduce the formation of the aqueous humour and so bring about a reduction in the iruraticular pressure, and are used in the treatment of glaucoma. See page 138 and Table 16.
carboplatin An analogue of cisplatin but with generally reduced side-effects, although the myelodepression may be more severe. It is used mainly in ovarian and small-cell lung cancer.
Dose: 40 nighn’ i.v. as a single dose, repeated after 4 weeks. Blood tests during treatments are essential. Severe renal impairment is a contraindication. ( Pai aplatin). See page 122 and Table 8.
carboprost A prostaglandin with a selective action oil the myornetrium, and used in post-partum haemorrhage not responding to ergometrine.
Dose: 250 pg initially by deep i.m. injection, with subsequent doses according to need up to a total of 2 mg (not for i.v. injection). Care in asthma, epilepsy and hypertension. Nausea and vomiting are side effects. (Hemabate).
carisoprodol A muscle relaxant used in niusculoskeletal disorders and muscle spasm.
Dose: I g daily. (Carisomi).
carmustine A cytoxic agent similar to 1-viustine. It is used mainly in brain tumours, multiple myeloma and Hodgkin’s disease, often in association with other drugs.
Dose: 200 rnghii2 by slow i.v, injection, repeated at intervals of 6 weeks. Side-effects are nausea, vomiting and burning at the injection site. A delayed bone-marrow depression is often a dose-limiting factor. (BICNU). See page 122 and Table 8.
Cef
carteolof A beta-adrenaergic blocking agent used as eye drops (0.1-0.2%) in glaucoma. Some systemic absorption may occur from eye drops, and care is necessary in asthma and bradycardia. (Teoptic). See page 138.
carvedilol A non-cardiac selective betablocker with the actions and uses of propanolol.
Dose: in hypertension 12.5 mg initially, rising to 25-50 mg as a single daily dose. (hucardic). See page 148 and Table 21.
cascara A mild purgative.
Dose: dry extract 100-250 nig, liquid extract and elixir 2-5 nil.
castor oil A mild purgative.
Dose: 5-20 nil. The oil has emollient properties and is used together with zinc ointment for pressure sores and napkin rash.
catecholamines A term applied to the synipathornimetic drugs adrenaline, dopamine, noradrenaline, and related compounds, indicating that they are derivatives of catechol.
CCNU See lomustine.
cefaclor An orally active cephalosporin antibiotic used mainly in urinary and respiratory infections.
Dose: 750 ing or more, up to 4 g daily, with reduced doses in renal impairment. Nausea and diarrhoea are side-effects, but all allergic reaction indicating sensitivity may require withdrawal of the drug. (Distaclor). SeeTable 34,
cefadroxil An analogue of cephalexin. It is well absorbed orally and gives high blood levels.
Dose: 1-2 g daily, (Baran), See page 248 and Table 34.
cefatnandole See cephamandole.
cefixime A cephalosporin with the actions, uses and side-effects of the cephalosporins generally, but effective in single daily doses of 200-400 mg. (Suprax). See page 248 and Table 34.
cefodizine A cephalosporin used in lower respiratory tract infections and in urinary tract infections.
Dose: 2 g (laity by i.m. injection or i.v.

Cefotaxime A cephalosporin with an ink reased activity against many Gram-negative organisms.
Dose: 2 g daily by injection, increased in severe infections tip to 12 g daily. A single dose of 1 g is given in gonorrhoea. The side-effects are those of the cephalosporins generally. (Claforan). See page 248 and Table 34.
cefoxitin A cephaniycin with a wide range of activity and an increased potency against Gram-negative bacteria. It is of value in many infections, and is also used in surgical prophylaxis.
Dose: 3-12 g daily by Lin. or i.v. injection. (NIefoxin). See page 248 and Table 34.
cefp1ronve A beta -lactaniase- stable cephalosporin with a wide range of activity. Dose: 2 g daily i.v. (Cefrom). See
page 248 and Table 34.
cefuroxime A cephalosporin often effective against some organisms resistant to penicillin, and with increased activity
against Haemophilus inflidenzae.    27 Dose: 3-6 g daily by injection. For surgical prophylaxis and in gonorrhoea a single dose of 1.5 g. Side-effects include nausea, diarrhoea, urticaria, rash and hypersensitivity reactions. (Zinacef). cefuroxime-axetil is an orally active form. Dose: 500 mg- I g daily. (Zinnat). See page 248 and fable 34.
celiprolol A selective 0, receptor blocking agent, with some stimulating action oil receptors. The former occur mainly in the heart, the latter in the bronchi and peripheral vessels. It is used in mild hypertension, as it has a vasodilatory and cardioselective action with reduced side-effects.
Dose: 200 mg daily, at breakfast. Occasional side-effects are nausea, headache and dizziness. (Celectol). See page 148 and Table 21.
ceflaodoxime An oral cephalosporin for respiratory tract infections.
Dose: 200-400 mg daily with food. (Orelox). See page 248 and Table 34.
ceftazidime A cephalosporin resistant to most beta-lactamases, and active against a wide range of Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa, although it is less active against Staphylococcus aureus. Valuable in both single and mixed infections.
Dose: 1-6g daily by injection, reduced in cases of renal impairment. In pseudontonal lung infections associated with cystic fibrosis, 1(4-150nit
g/kg daily. Side-effects include abdominal disturbance and local reactions at the injection site. (FortUol; Ket”adirn). See page 248 and Table 34.
cettibuten An oral cephalosporin similar to cefaclor, but with a longer action. Dose: 400 nigas a single daily (lose. (Cedax t. See page 248 and Table 34.
ceftriaxone A cephalosporin of the cefaclor
Jtype given as a single daily dose of I g by eep i.m. or slow i.v. injection, doubled in severe infections. With high doses vary injection site. (Rocephin). See page 248 and Table 34.
cephalexin An orally active cephalosporin Of value in infections of the respiratory and urinary tracts, and in naso-oral and soft-tissue infections.
Dose: 1-2 g daily, but lower (loses are indicated in renal impairment. Cephalexin is usually well tolerated, but sonic gastrointestinal disturbances may occur. (Ceporex; Kellex). See page 248 and Table 34.
cephalosporins A group of antibiotics with properties similar to those of the penicillins, but having a wider range of activity. Some are active orally, others may have to be given by injection.
Cefotaxime, ceftazidime and ceftizoxime have an increased activity against Gram-negative bacteria, but are less potent against Staphylococcus aureus and Gram-positive organisms generally. Cefititoxin is active against bowel organisms. An indication of the range and dose is given in the table on page 248. The higher doses are given in severe infections; reduced doses should be given in renal impairment. The main side-effect of the cephalosporins is hypersensitivity, and cross- sensitivity to the penicillins is not uncommon. Sensitivity to one is likely to extend to all members of the group. The cephalosporins call affect blood-clotting mechanisms.

Atopic Eczema (continued)

Monday, May 18th, 2009

Various other things can irritate the skin and make atopic eczema flare up:
• cold weather
• dry air
• long car journeys
• sweating heavily; clothes or shoes that trap sweat may also cause problems
• dust mites, which can act as an irritant, even if not an allergen
• tobacco smoke
• solvents and other chemicals encountered at work
• skin contact with fruit (especially citrus), vegetables, and sometimes other foods. The spray generated by peeling potatoes can even produce eczema on the face.
Anything which increases blood flow through the skin makes the itching worse:
• heat, especially a hot bath or being too hot in bed
• anger or embarassment
• hot drinks of any kind
• coffee, tea and alcohol because of the drug-like substances they contain
• vinegar and spicy foods
• chocolate, soy sauce, yeast extract, orange juice, tomatoes and other foods that are rich in amines (see p. 200).
Various changes in the body can make the eczema worse:
• teething, in babies
• colds and other viral infections
• in women, certain phases of the menstrual cycle.
Many eczema sufferers are aware that their skin gets worse when they are upset, stressed or anxious Oust before examinations, for example). Like other allergic diseases, atopic eczema is not primarily psychological but, once it has begun, psychological factors can play quite a big part.
The good news…
…for children and teenagers, is that if you have eczema as a child, your chances of developing acne during your teens are greatly reduced.
Contact dermatitis too?
People with atopic eczema can develop contact dermatitis (see p. 54) in addition to their existing rash. There is always this risk with regularly applying creams to your skin, especially anything containing fragrance or lanolin. Antihistamine and antibiotic creams also carry this risk.
Even the ingredients in the creams prescribed for eczema – such as moisturisers and steroids – can sometimes provoke contact dermatitis. Creams are more likely to contain sensitising ingredients than ointments. Very occasionally, the sensitivity is to a preservative or emulsifier that is widely used in different ointments and creams, which means that switching brands yields no improvement. Steroid suspended in petrolatum (white paraffin jelly) is the least likely to cause reactions.
The rash produced by contact dermatitis looks no different from atopic eczema, so this sensitivity will be far from obvious. It will just seem as though the atopic eczema is not getting better.
Talk to your doctor if you think there may be a problem of this kind. He or she can check by using the suspect cream on one side of the body, and a different-but-equivalent product on the other side. Patch tests (see p. 92) may also help to identify contact sensitivity.
Diagnosis
There are five separate aspects to diagnosis:
1 Is this really atopic eczema? There are no clear-cut tests for atopic eczema. Instead the diagnosis is based on a ‘points system’ – how many of the typical features of atopic eczema are present? The doctor adds them up, and if there are enough, then it’s atopic eczema. Sometimes all the typical features are there and this is obviously the right diagnosis, but in other cases there may be room for doubt. The doctor should rule out the possibility of contact
dermatitis (see p. 54), especially if you have eczema only, or mainly, on the hands.
2 What avoidable irritants are making the skin worse?
3 Is the eczematous skin infected? The signs of infection are usually clear, but not always, especially with fungal infections. Steroid creams can sometimes mask the overt signs of infections: if atopic eczema is not responding to treatment this possibility should be investigated.
4 Are there any allergic reactions to those infections? Or to the normally harmless microbes that live naturally on the skin (see p. 17)? Skin-prick tests or blood tests can reveal such allergic reactions where fungi are concerned. Adults with persistent atopic, eczema which is getting worse rather than better are the most likely candidates.
5 Are there allergic reactions (or other sensitivity reactions) to food, or to allergens such as house-dust mite?
This fifth aspect of diagnosis is where controversy is rife. Many dermatologists feel that atopic eczema is treated quite adequately with moisturisers (emollients) and steroid creams. The search for allergic/sensitivity reactions – in other words, for basic causes – seems unnecessary for most patients, or more trouble than it is worth. Indeed, some dermatologists believe that looking for such sensitivity reactions is actually mistaken because they are not basic causes (see p. 42).
Other specialists disagree, and feel that allergic/sensitivity reactions are a basic causative factor in atopic eczema. They concede that there are many false positives, but in their opinion, there are enough true positives in the skin-prick test results to make it worth sorting them out from the false positives. Except for patients with very mild eczema, such doctors prefer to identify and eliminate the root causes, if possible.
Patch tests are now used by some of these doctors (see p. 69) – yet another contentious issue! The time-honoured use for patch tests is in contact dermatitis, and there is a lot of resistance to using them for atopic eczema. Traditionally, the immune reactions involved in atopic eczema and contact dermatitis are seen as entirely different – the former involving IgE and being a quick reaction (identified by skin-prick tests), the latter involving other players and
Sweaty sock dermatitis
More correctly known as ‘juvenile plantar dermatitis’, this rash on the feet affects an awful lot of atopic children. It is frequently misdiagnosed as athlete’s foot, and treated with anti-fungal drugs. The important clue can be found by looking between the toes: if there’s no rash there, then it is not athlete’s foot.
being much slower (identified by patch tests). New research into atopic eczema shows this view to be overly simple (see pp. 18-19) – and it provides a rational basis for using patch tests.
If, as a patient or a parent, you are keen to search for fundamental causes, remember that this should never displace treatments to quell infection or moisturise the skin and restore its protective structure. When these treatments are neglected the whole problem can get far worse, because of the vicious circles that sustain atopic eczema.
Treatment
Treatment for atopic eczema has five possible angles:
1 calming the inflammation
2 avoidance of scratching and rubbing
3 caring for the skin and restoring its normal structure
4 treating infections
5 avoiding allergens.
One or more of these aspects may be neglected, depending on what kind of specialist you are seeing.
Calming the inflammation
Steroid creams are the mainstay of atopic eczema treatment because they calm the inflammation in the skin. The creams do carry a risk of side effects, but are safe when used correctly (see p. 147). An over-fearful attitude to steroids creams can mean that the eczema never gets under control, and this can mean using more steroids in the long run. When treating an outbreak of atopic eczema with steroid cream, it is vital to continue applying the cream until the ‘hidden healing’ has occurred (see p. 146) – don’t stop as soon as the skin looks better.
Promising alternatives to steroid creams now exist: these are tacrolimus and pimecrolimus ointments (see p. 147). Unfortunately they are much more expensive, and your doctor will probably prescribe them only if there is some pressing reason.
Tar-based ointments have a much milder anti-inflammatory effect, and can be helpful for areas of thickened skin. They were once widely used for atopic eczema, but are used less now, in part because they stain fabrics and smell unpleasant. Sometimes they irritate the skin, too, and there are concerns about safety: they contain carcinogens, and significant amounts are absorbed into the bloodstream. However no evidence has been found that these cause cancer, despite intensive searching.
Antihistamine tablets are sometimes used and while they
may not help the eczema much, some evidence suggests that
they could reduce the risk of asthma developing later (see p. 249).
Powerful drugs such as cyclosporin are sometimes used in
severe cases of atopic eczema, to damp down the immune
response. They are taken by mouth, and can affect other parts of the body, not just the skin. Very careful monitoring is needed.
Sunlight is often beneficial, because it suppresses the inflammatory processes in the skin. However, not everyone improves with sun exposure – some get worse. Careful experimentation is the only way to find out: build up the length of sun exposure very gradually, starting with less than an hour a day.
Medical treatment with UV (ultraviolet) light can produce the same effect as sunshine and suppress inflammation. This treatment may be prescribed, but you should not try it for yourself with a sun-lamp. In PUVA treatment, a plant-derived substance called psoralen is given by mouth, or applied to the skin, to enhance the response to UV light.
Kicking the scratching habit
Scratching is a substantial part of the problem in long-standing atopic eczema. Experiments with healthy people and mechanical ’scratching machines’ show that perfectly normal skin will erupt into eczema if it is scratched intensively.
There is no steroid cream powerful enough to counteract the effects of scratching. But if scratching stops, then the skin can –with the help of medication – heal up.
Note that ’scratching’, in this case, includes rubbing the itch (directly or through clothes; using a hand, wrist, chin, leg, foot, or any other part of the body), touching or picking at the skin, rubbing against sheets, furniture or another person, or using a towel, flannel or hairbrush to rub the skin. All these activities can be habitual and quite unconscious, if atopic eczema has been present for more than a few months – you just don’t realise you’re doing it most of the time.
For many with atopic eczema, another problem creeps in –scratching without itching. This may be just habit, a response to boredom, stress or anxiety, or even part of the family dynamics, in which scratching has become a form of emotional expression. Scratching alone can set off itching, and a scratch-itch-scratch cycle ensues.
The first step in combating scratching (for an adult or older child) is simply to notice how often scratching occurs. Doctors at the Chelsea and Westminster Hospital in London issue their patients with little hand-held counting devices (tally-counters), and ask them to press the button on the device every time they scratch or rub. Over a period of days, patients discover – usually to their own amazement – just how often they do scratch. The point of the exercise is simply to become conscious of the scratching impulse, and to notice the situations which typically provoke scratching. You could use a small pocket-sized notebook and pencil to achieve the same end.
Once this awareness has been gained, then you are in a position to break the scratching habit. The methods involved –called ‘habit reversal’ – were first developed by a Swedish dermatologist, Peter Noren. It takes about 2-4 weeks for most people, but the change is long-lasting. Most eczema sufferers find that they recoup their time investment rapidly, once they are free from the chore of dealing with chronic eczema.
When you notice that you are about to start scratching, and before the urge to scratch overwhelms you, take control and do something deliberate with your hands – for example, clench your fists, while breathing deeply and slowly. Think cool non-itchy thoughts. The urge to scratch may pass. If it doesn’t, then you can allay the itch by pinching the itchy area gently, or pressing your fingernail into it, or lightly applying a little moisturiser.
In the bath or shower, don’t use flannels, and never rub or scrub the skin. Dry off by gently patting with a soft towel.
The aim is to get scratching episodes down to fewer than ten per day. In achieving this goal, relaxation exercises, stress management techniques, hypnotherapy or autogenic training (see p. 222) can also be very helpful, especially if you sometimes scratch in tense situations.
With small children, the parents have to do the noticing. Most are unaware just how much their child scratches or rubs the eczema – babies often rub against the side of the cot.
Once the awareness is there, a child over four can usually be taught the habit-reversal technique described above. With a younger child, the parents must distract the child when scratching is imminent, by talking or playing. If the child is scratching while asleep, parents should pick the child up and, very gently, hold the child’s hands away from the body. Situations and activities which commonly provoke scratching should be avoided, or planned for. Give the child something to hold while dressing and undressing, for example – keep the hands busy. But never say ‘Don’t scratch’ – it usually has the opposite effect in the long run.
For the first four days and nights, while you are trying to break the scratching habit, the child should never be alone, even for a minute – someone who is able to distract the child from scratching should always be there, and awake. Fortunately, children lose the habit far more quickly than adults.
Keep a child’s fingernails very short, and smooth them with an emery board too, so that if any scratching does occur the effects are minimised. (Soft cotton mittens, to be worn at night, are often recommended, but the cotton itself can be used to rub the skin – observe your child carefully! The same is true of all-over cotton suits.)
For this anti-scratching programme to be effective in healing the skin, there must be a determined effort with drug treatment at
Will it clear up?
Small children with eczema generally grow out of it by the age of two. Those who have eczema after this age tend to show a big improvement at puberty. Sometimes, however, the eczema can disappear at puberty, only to reappear later: so continue to be careful with your skin.
Atopic eczema is frequently the first sign of a tendency to allergies (see p. 22). Given this early warning sign, parents should take steps to avoid allergies developing, or at least reduce their severity (see pp. 244-9). One small piece of good cheer: atopic eczema and life-threatening food allergies are very rarely found together.
People with both asthma and atopic eczema frequently notice that when one improves the other seems to get worse. There is no explanation for this as yet.
Moisturisers - how to use them
Moisturisers (emollients) do two things: they increase the amount of water in the skin, and they lubricate the skin, making it less brittle.
A moisturiser is designed to leave an oily layer on the surface of the skin which stops the skin’s natural moisture from escaping. The most effective preparations, from this point of view, are ointments made from white paraffin, such as Vaseline, which form an uninterrupted waterproof layer: these are sometimes called occlusives. They contain no water, unlike creams. Although a cream forms a less formidable barrier to the escape of moisture from the skin, it does provide some moisture itself, which can soak into the skin.
The most important thing is to have something that you like using, so that you apply it regularly. There are lots of moisturisers available, so ask the doctor for different ones to try.
Applying moisturiser well is crucial:
• Apply moisturiser before your skin gets dry, as a preventive treatment.
• There’s no need to rub in your moisturiser (this can be a form of scratching). Just apply it very lightly.
• A thin layer is all that’s needed. A thick layer keeps in heat which aggravates the skin.
• Always apply within three minutes of a bath or shower.
• In addition, apply every 3-4 hours during the day. Carrying moisturiser around with you is helpful – get a small tube of moisturiser for this purpose.
• Ask the doctor to prescribe moisturiser in large quantities, to make sure you have enough. But beware of infecting big pots with Staphylococcus bacteria and then reinfecting your skin. Pump-action dispensers are safer.
Moisturiser can also be smeared onto bandages which are then wound around the affected areas at night to reduce the itch – or you can use ready-made ‘wet-wraps’ (ask your doctor about these). As long as the bandages/wraps are immovable, they will reduce nocturnal rubbing and scratching.
Avoid lotions, and any non-prescribed creams, as they could be irritating to the skin. Choose bath oils with care – some contain alcohol which is an irritant.
the same time. You should be using a steroid cream of sufficient strength, twice a day, and plenty of moisturising treatment.
By taking this ‘Combined Approach’, as Dr Christopher Bridgett and his colleages at the Chelsea and Westminster Hospital call it, you should be able to clear the eczema completely, even if you have had it for years and have tried innumerable different treatments. Once this has been achieved, you can maintain an eczema-free state by watching carefully for any outbreaks of itching, redness or roughness, and treating them immediately with a short course of steroid cream (see p. 146).
Skin care
Firstly, avoid all the irritants which you think may affect your skin. Give clothes an extra rinse cycle in the washing machine, to remove all detergent. or use a non-detergent system such as Eco-balls or Aquaballs. Wash all new clothes before wearing them, to remove chemicals such as formaldehyde. Wear soft cotton or silk next to the skin.
Where eczema affects the hands, special care is needed (see p. 57).
Water can be both good and bad for eczema. When you soak in a bath, water is absorbed by the skin cells, which helps correct the dryness of the skin. But when you get out of the bath, and the skin dries, the outermost layer shrinks and develops microscopic cracks, making it even less waterproof than it was before. The way around this is to apply a moisturiser immediately after a bath or shower –gently pat the skin until partially dry, and apply the moisturiser immediately to trap the water in the skin.
For anyone with a severe flare of eczema, current recommendations are:
• soak in lukewarm water for 20 minutes, twice a day
• pat dry
• quickly apply steroid cream to the eczematous areas, then moisturiser over the top, and to all other dry-skin areas
• make sure the moisturiser goes on within 3 minutes of emerging from the water.
This works well for some people, but not all. For a few eczema sufferers, the effect of taking natural oils out of the skin (which soaking does, to some extent) may outweigh the benefits of putting water in. Or they could be sensitive to something in the tap water – the chlorine, perhaps, or pollutants. It may not be obvious that this routine treatment is not helping. As Dr Michael Tettenborn, a British paediatrician with long experience of atopic eczema, observes: ‘By the time they’re referred to me, children are usually on the standard regimen of two-soaks-a-day. One of the first things I do, as an experiment, is tell the parents to just bathe them once a week and use a moisturiser and tissues to keep them clean the rest of the time. Some children do a lot better after that.

Atopic Eczema

Monday, May 18th, 2009

Atopic eczema
A Greek word meaning ‘to boil over’ or ‘to erupt’ is the source of the medical term ‘eczema’. It refers, of course, to the way in which the skin erupts into a rash, but it could equally well describe the eruption of controversy around this disease. No other allergic disease is quite such a cauldron of dissent - indeed, even the question of whether it is an allergic disease remains unresolved. These controversies directly affect the treatment of atopic eczema, so it is useful to understand them if you or your child have eczema.
The disagreement begins with the question of what causes atopic eczema.
Let’s start with the one point that everyone agrees on: dry skin plays a fundamental role. Those with atopic eczema have dry skin, not just in the eczematous areas, but in other parts as well, sometimes all over the body. The skin cells are less efficient than normal skin cells at retaining water.
Everyone would also agree that there is inflammation of the skin – a reaction that is produced by the immune system. But when it comes to the question of what starts off the inflammation there are huge differences of opinion among specialists treating atopic eczema – these specialists include dermatologists, allergists and paediatricians.
Since people with atopic eczema are atopic (allergy-prone), and most have
huge amounts of the allergy antibody, IgE, going round in their blood, it might
seem plausible that an allergic reaction to some external item kicks off the
inflammation. And when skin-prick tests (see p. 91) to common allergens such
as house-dust mite are tried, there are usually a large number of positive results.
But many of these turn out to be false positives – when tested more directly,
the allergen concerned does not actually play a part in causing the skin symptoms.
This has led some specialists working with eczema, mainly dermatologists, to
What the words mean
Eczema is not a disease in itself. The word refers to a certain type of reddish rash — a rash which can be caused in a variety of ways. The type of eczema that affects people of an allergic disposition (atopics), is called either atopic eczema or atopic dermatitis.
The word dermatitis just means inflammation of the skin. Most doctors consider it to be synonymous with eczema, but some give it a slightly broader meaning.
believe that allergic reactions play little part in either initiating or perpetuating atopic eczema. In their view, the basic cause of atopic eczema is dry skin and a generally overwrought immune system, not specific allergic reactions.
To some of these doctors, positive skin-prick tests are all false positives in atopic eczema – that is, irrelevant to the disease process. A positive skin-test result, in their opinion, simply indicates that the skin of atopic eczema sufferers is in a highly sensitive state, not that the allergen concerned plays any causative role.
Allergists tend to take a different view of this, as you might expect. And recent research shows that they are correct – allergens often do play a significant part in provoking atopic eczema.
Research using direct challenge tests (see p. 90) has identified some of the things that could provoke such sensitivity reactions:
• house-dust mites, pollen or moulds
• cats, dogs, rabbits and other furry pets
• cow’s milk or other food – a prime suspect in babies and young children (see p. 68). The response to food is usually delayed, occurring some hours after the item is consumed.
With mite, pollen and pet allergens, the eczema symptoms can be provoked either by allergens falling on the skin, or by direct contact (e.g. mite allergens in the bed, skin contact with pets, or lying on grass for those with grass-pollen allergy).
The rash tends to occur on skin not covered by clothes, as you would expect. But it can sometimes occur only on particular exposed areas – usually the most sensitive areas of skin. For example, there are people who react to house-dust mite but have eczema on the eyelids only.
Additionally, experiments show that even when an airborne allergen is only inhaled it can sometimes provoke eczema symptoms. The allergen probably reaches the skin in the bloodstream. (Alternatively, it might provoke an immune reaction in the airways which generates chemical messages of the kind that promote inflammation – these then reach the skin in the blood.) This means that the skin reaction could occur anywhere on the body, not just on exposed skin.
In the case of food, the molecules of food that cause the trouble are probably being absorbed from the stomach without being completely broken down. They then reach the skin via the blood to provoke a reaction there. (Or, again, it could be an inflammatory messenger chemical travelling from the gut to the skin in the blood.)
When food gets directly onto the skin – which it frequently does with small children, of course – it can provoke a reaction that way too. This may be a slow eczema-causing reaction, or a much faster reaction known as contact urticaria (see pp. 50-51). Reacting to food with contact urticaria is quite common in children with atopic eczema – but the same food doesn’t necessarily provoke atopic eczema when it is eaten. (However, eating these foods can sometimes trigger anaphylaxis – see pp. 58-9. They should therefore be treated with great caution.)
At the same time as all this research – which shows for sure that allergens play a part in atopic eczema – others have been asking what actually happens when skin reacts to an allergen. Their studies have turned the accepted understanding of allergies upside-down. They show that when something like egg or pollen provokes atopic eczema, what is occurring isn’t necessarily an allergic reaction of the usual sort, with IgE and mast cells (see
box on p.12). Instead, other immune cells are causing the trouble. Sometimes IgE is involved, but without mast cells. Sometimes neither is involved. These revolutionary discoveries are described in more detail on pp. 18-19. One interesting realisation from this research is that in different eczema sufferers, different immune reactions may be producing the rash – even if they are reacting to the same allergen! This helps to explain why the results of skin tests are so inconsistent and puzzling.
The wandering rash
For a baby with atopic eczema, the face, and especially the cheeks, are commonly affected, but there may be a rash all over the legs, the backs of the arms, and the back. As the months go by, the rash settles on the lower legs, and spreads to the fold of the elbow, and then the fold at the back of the knees — by about three years of age, this flexure eczema is the main problem for most children.
In adults, eczema is often found in quite restricted areas, such as the hands, scalp, lips, eyelids or chest. It may be located around the nipples — a sensitive spot where rubbing by clothing is enough to initiate a rash.
Atopic eczema is always in a process of change, and different parts of the body may display different stages of the rash:
• The rash is red and usually dry at first, and there may be not a great deal to see. In this early stage the visible signs may be minimal, while the itchiness can be colossal. Sometimes there is oozing of clear fluid.
• Occasionally the first phase is more marked, with dense patches of small red bumps or tiny blisters. On the hands, these may merge to form larger blisters.
• Infections tend to change the appearance of the rash (see p. 44).
• With time the skin becomes thicker, paler and scaly. It may form leathery patches (called lichenification), especially if there is habitual scratching or rubbing. This is chronic eczema.
• When the eczema clears, there may be an area of skin that is lighter in colour, or darker, than the surrounding skin.
The next step
Whatever causes atopic eczema, it provokes the most horrendous itching, as every eczema sufferer knows. The itch cries out to be scratched, and scratching is the major cause of the visible rash. If left untouched, the skin does not erupt into eczema, although it may well turn red, and there are still distinct changes in the skin that can be seen with a microscope.
Once eczema has erupted, the skin is no longer an intact protective layer that neatly separates ‘in-here’ from ‘out-there’. The skin becomes more permeable and loses its own natural moisture far more readily, so the dryness gets worse. At the same time allergens and irritants penetrate far more easily, causing yet more inflammation.
Something else compounds the damage: once atopic eczema is established, the immune system starts making IgE antibodies to the body’s own proteins, especially those found in skin cells. This helps explain why atopic eczema can become so severe and so entrenched.
Infections — another vicious circle
When eczema erupts and the skin barrier is breached, infections often become a problem. A regular source of trouble is the bacterium Staphylococcus aureus, a cause of the infection impetigo. This microbe invades eczematous skin far more readily than healthy skin, causing a prolific ooze with golden-yellow crusting.
Staphylococcus aureus produces a toxin known as a ’super-antigen’ which revs up the immune system to even more furious effort. This effort does not, unfortunately, oust the bacteria, but it does make the skin inflammation even worse. To add to their woes, many who are afflicted with atopic eczema start making IgE antibodies against Staphylococcus aureus toxins.
Infection with fungi (yeasts and moulds) is also a problem in atopic eczema (see p. 49), and there may be sensitivity reactions to these fungi.
The herpes virus, responsible for causing cold sores, can also invade eczematous skin, though this is much rarer. It worsens the eczema and produces fever and general weakness. There may also be flocks of small red bumps, each with a tiny dimple or blister at the centre. Any symptoms of this kind indicate that the patient needs urgent treatment.
Irritants and stress
People with atopic eczema are far more susceptible to everyday irritants such as wool and rough synthetic fabrics, soap, and traces of detergent left behind in clothes. Chlorinated water, either in swimming pools or from the tap, can also aggravate the skin, and even ‘hard’ water (found in areas with chalk or limestone bedrock) may be a factor.
Some air pollutants may play a part in atopic eczema. Researchers in Germany have found that children living close to busy trunk roads, or in homes with a gas cooker and no extraction hood (see pp. 128-9), were more likely to develop eczema. Formaldehyde fumes, often found in modern houses (see p. 129), are sometimes a factor when eczema affects the face and hands.

DISCOVERIES ABOUT ALLERGY AND SENSITIVITY

Monday, May 18th, 2009

`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 .