The epidemic of eczema, which affects one fifth of children, may be the fallout from our obsessive concern with keeping our children free of germs.

Eczema is now a worldwide epidemic. In the UK, up to one fifth of school age children and one in 12 adults suffer from it. It is itchy, painful, reduces the quality of life and has no cure.

Also known as atopic dermatitis, eczema forms part of the ‘atopic triad’, a group of disorders including allergies and asthma all of which are becoming increasingly common. Each of these conditions is thought to be a different manifestation of the same internal chaos, and they commonly appear in the same person all together at the same time or serially.

Some argue that without a clear understanding of the cause of a disease, it is impossible to provide effective treatment eczema appears to be a good argument in favour of this idea. Treatment, usually with ointments and creams, topical steroids, antibiotics and antiinflammatories, can be hamfisted or hit and miss. Most of these treatments are poorly researched (Health Tech Assess, 2000; 4: 1-191), not suitable for long term use and certainly not safe for children. Often, they will appear to work for a short time before the disease flares up again even worse than before.

Just how poor most eczema treatments are was illustrated last year at a meeting of the American Academy of Dermatology. There, Dr Amy S. Paler, professor of dermatology at Northwestern Medical School, revealed the results of a study on patient satisfaction with conventional eczema medications.

In a study which surveyed the parents of 429 paediatric eczema patients, one third of parents considered the medications prescribed for their children ineffective (Skin Allergy News, 2000; 31: 29). According to Dr Paler’s results, prescription medications such as the topical corticosteriods betamethasone dipropionate, clobetasol propionate, hydrocortisone and mometasone furoate were considered not effective (32 per cent), somewhat effective (26 per cent) and fairly effective (23 per cent). Only 19 per cent of parents felt that the medications were very effective for their children. This held true even when the medications were considered to be moderate to high potency.

Non prescription remedies did not fare much better. Asked to judge agents containing hydrocortisone, 36 per cent of parents rated them as not effective, 57 per cent said they were somewhat effective or fairly effective, and only 7 per cent found them to be very effective.

Apart from being ineffective, topical steroids bring other problems, such as allergic skin reactions (J Dermatol, 1991; 18: 454-64; Skin Pharmacol, 1992; 5: 77-80), bone and organ damage (Dermatol Clin, 1992; 10: 505-12; Lancet, 1995; 345: 330), permanent adrenal suppression (Zeitschr Hautkrankh, 1988; 63: 302-8), eye damage (Br Dermatol, 1989; 120: 427-3; Eye, 1993; 7: 664-6) and damage to vital organs such as liver and kidneys. While it behooves us to find safer alternatives, no such initiative has yet taken place (see box, page 4 ).

The hygiene hypothesis

The causes of eczema are many and varied. It is thought that the tendency towards atopy is inherited, and that it involves an excessive immune reaction to allergens in the environment. The link between eczema and food allergies is well established in the literature, yet few physicians use restrictive diet or test for allergies as a first line treatment. But if the link between food and atopy is rarely acted upon, the link between childhood drug use and atopy is positively ignored.

Yet the development of eczema has been linked to several drugs given routinely to children, including vaccinations, antibiotics and paracetamol.

This idea forms part of the ‘hygiene hypothesis’ which says that by ‘protecting’ children from exposure to dirt and germs, and by preventing disease from taking its full course in childhood, we are inadvertently destroying the immune system’s ability to respond appropriately to infection and other stimuli.

During most of our evolution and from the moment of birth, our bodies are exposed daily to dirt and germs. It is thought that this exposure helped forge and maintain the immune system’s sophisticated network of chemical pathways and specialised cells. According to the hygiene hypothesis, without the early input of dirt and germs, the immune system cannot respond appropriately when challenged.

The hypothesis came into being in 1989, when David Strachan, an epidemiologist at the London School of Hygiene and Tropical Medicine, noticed that children from large families where infections are likely to circulate freely were less likely to develop atopy (BMJ, 1989; 299: 1259-60).

His ideas were heresy to most doctors who believed that infections triggered allergies, not protected us from them. Some continue to resist this idea and argue that routine jabs have ‘saved’ us from killer diseases such as polio and tetanus. But, the other side of the argument is that they also provide the wrong sort of stimulation to the immune system. Instead of strengthening it, they overstimulate one part at the expense of another, leaving us even more vulnerable to allergies and other immune problems.

In the intervening years, the hypothesis has been more fully developed. While the common media interpretation of the hygiene hypothesis is that childhood diseases train the immune system to respond vigourously to stimuli, Graham Rook, an immunologist at University College London, says this is rather too simplistic. He also points out that the name ‘hygiene hypothesis’ is misleading since hygiene per se is not a bad thing and, indeed, better hygiene is responsible for many gains in human health. It is obsessive measures toward cleanliness, killing germs and suppressing illness that are problematical.

In the hygiene hypothesis, atopic diseases form part of yet another triad that includes immune diseases such as MS and insulindependent diabetes, and inflammatory bowel diseases such as ulcerative colitis and IBS.

“In each case,” says Rook, “it is not that the immune system isn’t working, but that it is working too well. Often it is overresponding to minimal amounts of stimulus and to things which should never elicit an immune response. What’s missing is the mechanism which shuts the immune reaction off.”

The data on vaccination and atopy are remarkably consistent. There are studies showing that the more exposure to infections such as tuberculosis (Science, 1997; 275: 77-9), measles (Lancet, 1996; 347: 1792-6) and hepatitis A (BMJ, 1997; 314: 999-1003), the less the atopy.

In one study of children who received the DTP (diphtheria, tetanus and pertussis) and polio vaccines, 23.1 per cent had asthma episodes, 22.5 per cent had asthma consultations, and 30 per cent had consultations for other allergic illnesses (Epidemiology, 1997; 8: 687-80).

In a more recent study from the UCLA School of Public Health, the DTP vaccination was again shown to increase the incidence of allergies. The risk of having a history of asthma was twice as great among those who received the vaccine, with the highest risk in children who were 5-10 years of age.

In yet another study in Oxford, vaccination with whole cell pertussis vaccine was significantly associated with development of atopic disorders (Thorax, 1998; 53: 927-32). This study also found

a significant relationship between childhood antibiotic use and the development of atopy (see below).

However, a new Finnish study one of the largest ever conducted suggests that early exposure to what the researchers called ‘natural measles’ was not protective against atopy (Lancet, 2000; 283: 343-6).

A closer look at the data, however, reveals an interesting definition of ‘natural measles’. The study was based on data from 547,910 children, aged 14 months to 19 years at the time of a mass MMR vaccination campaign (1982-1986) in Finland. Data on atopic conditions was collected at the time of the campaign and showed that while 20,690 children reported having measles, 52,087 reported having eczema, 17,131 had allergic rhinitis and another 10,058 had asthma.

However, it was older children (aged 8 and up) who were most likely to have reported measles before the vaccination children who may have been on the receiving end of the single measles vaccine, which was the standard from 1975 to 1982 and given to as many as 70 per cent of Finnish children.

The authors did not disclose information on previous vaccination history but, among such children, measles infection is anything but natural. It may be caused by mutations of the disease due to the vaccine or, equally, it may be such a mild disease that it does not fully ‘challenge’ or develop the immune system.

Commenting on the study (Lancet, 2000; 283: 394-5), Drs James E. Gern, University of Wisconsin Medical School, and Scott T. Weiss, Harvard Medical School, suggest that while the study was large, its parameters were too narrow to be conclusive ,and that it was probably exposure to infectious diseases in general particularly lower respiratory tract infections and not just to measles that is protective against atopy. Say the authors, “Measles infection is not a good indicator of overall exposure to infectious disease in a Western environment such as Finland.” They also note that other factors, such as the timing of infection, may also be relevant.

Germ phobia

High uptake of childhood vaccinations, of course, mirrors an increasing decline in breastfeeding, found to protect against many childhood disorders such as eczema as well as colds and other infections. It’s an important point since a non breastfed child is more likely to succumb to such diseases and, in our germphobic culture, more likely to be given medications such as antibiotics and NSAIDs to ‘fight’ the bug and its symptoms.

Both antibiotics and NSAIDs such as paracetamol (a prime ingredient in many infant suspensions) are also associated with the development of eczema.

Antibiotics, of course, are sometimes given in combination with steroids as standard therapy for eczema. The rationale behind this is that the open sores common to eczema may become infected. However, continual use of antibiotics can cause Candida overgrowth which can actually make the eczema worse.

Antibiotics taken for other reasons may be similarly damaging. In a study in Belgium, data were collected from 1206 six and seven year old children who were not exposed to antibiotics in the first year of life, and 675 children who were. The use of antibiotics early in life was found to be significantly associated with atopy in children who had a family history of the disorder (Clin Exp Allergy, 2000; 30: 1548-53).

An intriguing observation is that eczema rates have increased in line with sales of paracetamol. Paracetamol use has already been associated with an increase in asthma and rhinitis in young adults. Researchers at King’s College London performed an analysis to see if there was any link between paracetamol sales and atopic disease prevalence in children and adults.

They used data from the International Study of Asthma and Allergies in Childhood (ISAAC) on the prevalence of four atopic symptoms in 13 and 14 year olds and 67 year olds in 1994-1995 as well as data from the European Community Respiratory Health Survey (ECRHS).

Not surprisingly, they found that paracetamol sales were high in English speaking countries. But what was surprising was that paracetamol use was positively associated with asthma, eczema and allergic rhinoconjunctivitis in teenagers, and wheeze and asthma in older individuals (Eur Resp J, 2000; 16: 817-23). The risk went up as the dose went up.

Even more intriguing is the hypothesis that the decrease in paediatric aspirin use (due to the risk of Reye’s syndrome) in favour of paracetamol may also be a contributing factor. Aspirin, in contrast to paracetamol, sets off chemical reactions in the body that suppress immunological T-cell responses (Ann Allergy Asthma Immunol, 1998; 81: 347-51).

If all this seems too much to take on board, consider that atopy is much less common in children who live in somewhat less sanitary conditions such as farms (Clin Exp Allergy, 1999; 29: 28-34) and in those whose families are not obsessive about handwashing (see box, p 3). There is also growing evidence that children in large families where diseases get spread around early in life have less atopy (Thorax, 1998; 53: 28-32; BMJ, 1994; 308: 692-5). Also, children from small families who enter daycare at an early age also seem to get the same protection (Lancet, 1999; 353: 450-4).

Add to this the finding of a recent Swedish study, that children in families who follow an anthroposophic life style avoiding unnecessary antibiotics, having few vaccinations and diets which include live lactobacilli have lower rates of atopy (Lancet, 1999; 353: 1485-8), and the hygiene hypothesis begins to look increasingly sound.

Newer thinking is that if eczema is to be approached with any drug treatment at all, then drugs should seek to activate certain pathways within in the immune system to keep it from overreacting. Such therapy is similar to the desensitisation regime which homoeopaths have been advocating for years.

Studies are in progress to assess the effectiveness of a ‘vaccine’ that might do the job which natural dirt and diseases were supposed to do. Experiments based on animals given a vaccine based on Mycobacterium have been encouraging (Immunology, 1998; 93: 307-13) although, of course, it is difficult to draw firm conclusions about human health from animal studies.

You can’t help but wonder whether a campaign to educate parents on the benign nature of most household germs and the benefits of childhood illnesses might be a cheaper and more effective way to protect future generations.

!APat Thomas

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