Prevention




(1)
Department of Dermatology and Allergology Biederstein, Technische Universitaet Muenchen (TUM), Munich, Bavaria, Germany

(2)
Christine Kuehne Center for Allergy Research and Education (CK-CARE), Hochgebirgsklinik (High Altitude Hospital), Davos, Switzerland

 



In addition to general activities to promote health, prevention recommendations comprise:



  • Primary prevention


  • Secondary prevention


  • Tertiary prevention (Fig. 6.1)

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    Fig. 6.1
    Various levels of health promotion and prevention of disease


6.1 Primary Prevention


The basis of rational recommendations for primary prevention of allergy or eczema is precise knowledge about causes and mechanisms of the development of these conditions as well as methods for the definition of possible risk groups (Von Hertzen and Haahtela 2010) (see Chaps. 1, 2, and 3).


6.1.1 Risk Groups


In all recommendations for primary prevention, it has to be distinguished between strategies involving the whole population and those which are only recommended for risk families (Wahn and von Mutius 2001).

The most simple way to define allergy risk is family history, i.e., children whose parents are suffering or have suffered from an atopic disease (one or both parents) are at greater risk. Measurable laboratory biomarkers from cord blood have been investigated but—in spite of progress in molecular genetics and experimental immunology—are not yet available for routine purposes such as T-cell subpopulations, phosphodiesterase concentrations in mononuclear cells, IgE or IgE receptor expression, filaggrin mutation, etc.


6.1.2 Allergy Development


Our knowledge regarding causal factors in allergy development is limited and comprises, apart from allergen exposure, anthropogenic and biogenic influences from the environment, which can act as modulators either in a protective or an enhancing sense (see Sect. 1.​5). The avoidance of allergy-enhancing factors might make sense in primary prevention.

Current recommendations comprise avoidance strategies, preferably regarding nutrition, but also other environmental factors from indoor and outdoor air. An S3 guideline in Germany for primary allergy prevention has been recently actualized (Schäfer 2002; Schäfer et al. 2004a, b; Muche-Borowski et al. 2010).

Prevention strategies regarding nutrition and diet are covered under “hypoallergenic infant formula” and “nutrition.”


6.1.3 Avoidance Strategies and General Recommendations



6.1.3.1 Pet Keeping


While over decades the classical recommendation was to strictly avoid fur- and feather-bearing animals in the house, a variety of recent studies have brought new evidence in a more differentiated way. It has been shown that persons with extremely high contact to pets (maximal cat allergen exposure in indoor air corresponding to several cats) may develop protecting antibodies (quoted in Muche-Borowski et al. 2010; Schäfer et al. 2008).

Still the recommendation to avoid cats is actual. This may be different with regard to dogs. There are studies which show a decreased allergy prevalence in families where dogs are kept. Therefore, the strict recommendation to avoid dogs is no longer relevant. With regard to the mechanisms, it may be speculated that dogs with their natural “coprophilic” behavior can alter the microbiome in the family environment!

For the general population, there is no reason to restrict pet keeping with regard to primary allergy prevention. In this context, these strategies comprise allergies in general and are not specific for atopic dermatitis. There is, however, also no reason to keep pets for allergy prevention!


6.1.3.2 Farming Environment


One of the most exciting findings in the past has come from studies performed in the alpine regions of Bavaria, Austria, and Switzerland, where it has been found that living and growing up on a farm seemed to be protective with regard to the development of airway allergy (Riedler et al. 2001; von Mutius and Vercelli 2010; Alfvén et al. 2006; Illi et al. 2012). It was interesting that a special type of farming culture with traditional farming (cows and cultivation) was protective, as well as the number of different species kept on a farm seemed to be important in the sense of “diversity” as a protective element.

Particularly pronounced were the effects when the mother of a child had worked in the stable during pregnancy (Roduit et al. 2012; Ege et al. 2008a).

Regarding nutrition on the farm, see below.


6.1.3.3 Use of Parasite “Worms” in Atopy Prevention


According to the “jungle” or “hygiene” hypothesis, immunodeviation toward Th2 reaction pattern occurs when the natural stimulation of the immune system by parasitic infestation is lacking due to improved hygiene (Ring 1982a, b; Strachan 1989).

Therefore, people have tried to induce similar immunomodulating effects by applying worms or helminth substances in order to decrease Th2 reactions.

There are already clinical trials with parasites of the species Trichuris as well as Necator americanus. Most of the studies are still experimental; however, first clinical trials have not shown convincing effects (Bager et al. 2010).

A recently published study described a good therapeutic effect of a compound named IPBD WB1001 as a small molecule having shown to inhibit proinflammatory cytokines and T-cell migration. This compound was extracted from bacteria living in entomopathogenic nematodes (2-isopropyl-5-(E)-2-phenylethenyl-benzene-1,3-diol) (Bissonnette et al. 2011).


6.1.3.4 Aeroallergens


In the indoor air, where human beings spend most of their lifetime, it is advisable to produce a climate which does not favor mold growth, i.e., too high humidity and poor ventilation.

Exposure against house dust mites, especially in the bedroom, may play a role for allergic individuals; however, for primary prevention, reduction of mite exposure has not shown effective evidence.


6.1.3.5 Air Pollutants


The major air pollutant in the indoor air is derived from environmental tobacco smoke. Many studies have shown increased allergy and eczema prevalence rates in children passively exposed to tobacco smoke (Schäfer et al. 1997b; Krämer et al. 2004; Wang et al. 2008). Therefore, avoidance of smoking not only for the mother and during pregnancy but also generally for the family is one of the most important recommendations for primary allergy prevention.

In the outdoor air, pollutants derived from car traffic exhaust are most relevant, especially fine and ultrafine particles, which has been shown in children living close to a heavy traffic road (Kraemer et al. 2001; Morgenstern et al. 2008; Lee et al. 2008). Therefore, it is recommended to keep exposure against traffic exhaust as low as possible.

Apart from the alpine farmer’s story, there is evidence from other studies that Western lifestyle is associated with increased allergy and eczema prevalence according to the hygiene hypothesis (Strachan 1989; Ring et al. 2001b) (see Sect. 1.​4).


6.1.3.6 Vaccination and Immunomodulatory Strategies


One of the questions most often asked by mothers in daily practice is whether their children can be vaccinated. There are rumors that “natural infection,” e.g., with measles virus, may be more protective and more “healthy” than the vaccination. There is a great deal of philosophical involvement in these debates. Once, a very nice and intelligent father of such a religious community told me that “there must be some reason for these childhood infectious diseases in evolution and some benefit for mankind.” Not very politely, I answered “Yes, you are right, there is indeed a reason, namely there is a clear-cut effect against overpopulation.”

Fact is that adequately performed vaccinations do not increase the allergy risk, neither for airway nor for skin atopy. Of course, vaccination should not be performed during an acute flare of the disease. Therefore, all children with atopic dermatitis can receive the normal vaccinations like other children! The second most asked question regarding egg allergy and vaccinations produced on eggs also can be answered clearly: “There is no contraindication for these vaccinations; in children with severe egg anaphylaxis it is recommended to test the vaccine prior to application.”

The effect of immunomodulatory strategies such as application of pre- and probiotics will be covered below (see Sect. 6.1.4.6).

Furthermore, there is no evidence for a clear-cut association between application of antibiotics and development of atopic diseases (Muche-Borowski et al. 2010). Therefore, there is no need to avoid antibiotics when they are necessary.


6.1.3.7 General Recommendations


General recommendations for primary prevention—also for secondary and tertiary prevention—comprise avoidance of irritants of all categories (see Table 6.1). This includes clothing, skin hygiene, jewelry, etc. (Frosch 1985; Schwanitz 1992; Langan et al. 2009). A recent study found that nylon clothing, dust, and shampoos may play a role as triggers of eczema flares in children (Langan et al. 2009).


Table 6.1
General avoidance of irritant factors













Skin-irritative clothing, wool, nylon, too vehement skin cleaning, too early use of potentially sensitizing jewelry, e.g., nickel ear piercing

Airways (dust, fog, air pollutants such as tobacco smoke, traffic exhaust, volatile organic compounds VOCs, etc.)

Nutrition (irritative or directly pharmacologically active compounds such as too hot spices, alcohol, etc.)

Psychosocial (unpleasant mental or emotional stress)

An epidemiological trial had found an association between increased water hardness and eczema prevalence in the UK (McNally et al. 1998). However, the use of ion-coupled water softeners does not seem to have enough evidence to be recommended as a primary preventive strategy (Gamble and Dellavalle 2011).


6.1.3.8 Pharmacological Primary Prevention


Attempts to induce primary prevention with pharmacological substances such as histamine antagonists have not shown the desired effect as was found in the ETAC (Early Treatment of Atopic Child) study when the infants were treated with cetirizine at first signs of atopic dermatitis over 2 years (Diepgen et al. 2002).


6.1.3.9 Summary


Recommendations for primary prevention comprise dietary recommendations as well as avoidance strategies and general considerations. In the last years, these recommendations have been less rigid with regard to pet keeping: While cats should still be avoided, dog keeping does not seem to go along with an increased risk of allergy but may even have protective effects. However, there is no indication for the general population to keep pets for allergy prevention.

Indoor climate conditions of too high humidity allowing mold growth should be avoided. The most important recommendation with regard to air pollutants is avoidance of tobacco smoke in the indoor air and traffic exhaust in the outdoor air. There is no reason why atopic individuals should not be vaccinated like normal children. Interesting results from epidemiological trials such as in remote islands or alpine farm environments are very important for research but cannot be translated easily into practical prevention recommendations.


6.1.4 Nutrition and Dietary Recommendations



6.1.4.1 Breastfeeding


The longest-known and scientifically best investigated recommendation for primary allergy prevention starts at birth and includes strict breastfeeding from day 1. From epidemiological investigations as well as animal experimental studies, it is known that, in the first month of life, there is a special “window of opportunity” during which an organism can develop tolerance against environmental substances (Akdis et al. 2000; Blaser 2008; de Weck 1995; Wahn and von Mutius 2001; Høst et al. 2008; Burks et al. 2008).

Breastfeeding thus is the only “general antiallergic diet” which can be recommended; however, the effect is limited and does not last very long. Therefore, the recommendations comprise only the first 4 months of life (Muche-Borowski et al. 2010). Whether the positive effect of breast milk corresponds only to allergen avoidance, namely, of cow proteins, or whether there may be active protective factors in breast milk is a matter of speculation.

The fact that in breast milk also small amounts of allergenic proteins depending upon the maternal diet may be detected implies dietary recommendations for lactating mothers. In Scandinavian studies, a certain effect of oligoallergenic diet during lactation has been observed (Hattevig et al. 1999).

In the last years, the evidence regarding breastfeeding and prevention of eczema has been more and more controversially discussed. There are also studies which show increased rates of eczema in breastfed children, and meta-analyses have concluded that there was no convincing evidence of a protective effect of exclusive breastfeeding in eczema (Flohr et al. 2011).


6.1.4.2 Solid Food in the First Year of Life


With regard to the introduction of solid food, the recommendations have changed slightly: While previously introduction of solid food was recommended only after the sixth month, this has now been shortened to the fourth month of life. There is no evidence of a definite preventive effect of delayed introduction of solid food. Also a certain diversity of food groups—with special emphasis on yoghurt—seems to be helpful (Roduit et al. 2012).


6.1.4.3 General Recommendations


There is no general antiallergic diet. There have been studies showing that regular consumption of fish already in the first year of life may have a protective effect. Generally, Mediterranean diet with a high amount of polyunsaturated fatty acids may have beneficial effects (Chatzi et al. Thorax 2008 neu). This also holds true for dietary recommendations during pregnancy.

Generally also obesity seems to be a risk factor for asthma. Therefore, normal diet and avoidance of obesity is also recommended (Bouther and Sutherland 2007).

It is important that the diet in the first year of life contains all the necessary elements and vitamins and a certain degree of diversity according to general nutrition recommendations (Fig. 6.2). There is a shift in paradigm from strict avoidance to induction of tolerance by targeted application (Dutoit et al. 2008).

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Fig. 6.2
Dietary schedule for healthy nutrition in the first year of life (With friendly permission of C. Kugler)


6.1.4.4 Nutrition During Pregnancy


For the time during pregnancy, recommendations are difficult and generally controversially discussed (see probiotics); there is limited evidence from prospective clinical trials.

Mostly nutrition for a pregnant woman is not easy and connected with a lot of problems. Therefore, it is important not to make it more difficult. Most important is avoidance of smoking (see above) and too much calories (control of body weight), since obese pregnant women tend to give birth to overweight children. New studies have shown that increased body mass index is associated with higher prevalence of asthma (Warner 2009). There are no good studies with regard to atopic dermatitis.

Avoidance of overweight has therefore been included in current dietary recommendations for allergy prevention (Muche-Borowski et al. 2010).

Possible regular intake of fish—probably because of high amounts of polyunsaturated fatty acids—during pregnancy and lactation may have beneficial effects (Dunstan et al. 2004).


6.1.4.5 Hypoallergenic Formula


Whenever breastfeeding is not possible for one or another reason, there are a variety of “hypoallergenic” infant formulas which can be used as a supplement to cow’s milk (Vandenplas et al. 1995).

The term “hypoallergenic” can only be used when certain requirements are fulfilled by law, i.e., among others a concentration of allergenic protein of less than 1 % in the original product in Germany. From the point of view of food technology, mostly hydrolysis is used to achieve these levels by either enzymatic digestion, ultrahigh temperature, or ultrafiltration. Therefore, also the term “hydrolysate formula” is used. Apart from the chemical nature of the major ingredients of the original material, namely, casein or whey molecules, the intensity of the hydrolysis, which can lead to either partially or extensively hydrolyzed food, is crucial. Earlier mostly weak hydrolysates had been used for prevention, while extensively hydrolyzed formula are only given when there is already existing cow’s milk allergy.

Among many studies with regard to the efficacy of hypoallergenic infant nutrition in allergy prevention, the GINI study (German Infant Nutritional Intervention) has yielded quite reliable results. More than 2000 newborns were investigated in a prospective randomized and double-blind study. Apart from a control group, one group was exclusively breastfed, and three groups received hydrolysate formula of different degrees. As parameters of outcome, the occurrence of atopic dermatitis, food allergy, or urticaria was observed (von Berg et al. 2003, 2008). The group with exclusive breastfeeding was not included in the final evaluation since for ethical reasons neither randomization nor blinding could be performed here. However, it is interesting that some of the extensively hydrolyzed formula had a similar allergy-preventive or even better effect than exclusive breastfeeding. The formula groups received are the following:



  • Partially whey


  • Extensively hydrolyzed whey


  • Extensively hydrolyzed casein

In a careful analysis of the results, the authors came to the conclusion that there is a preventive effect of hypoallergenic infant formula which, however, does not seem to depend solely on the degree of hydrolysis or the nature of the protein but rather on the final total preparation and also the susceptibility of the infant (regarding family history of atopic dermatitis) (von Berg et al. 2003, 2008). In children with familial occurrence of allergy in general, however, and no atopic dermatitis in near first-grade relatives, hydrolyzed formula of all three groups showed a preventive effect with reduction in prevalence of atopic dermatitis by around 50 % compared to normal cow’s milk baby formula.

However, when there was atopic eczema in the family, the weak and extensively hydrolyzed whey products were no longer effective, but only the extensively hydrolyzed casein product was able to reduce the incidence of atopic dermatitis by 50 %.

Apart from hypoallergenic products, there are allergen-free amino acid mixtures (e.g., Neocate) which can also be given as therapeutic nutrition (see Table 6.2).


Table 6.2
Therapeutic nutrition (extensively hydrolyzed or amino acid formulas, which can also be used in infants with existing cow’s milk allergy)




























Protein nature

Product

Whey hydrolysate

Alfaré (Nestle), Althera (Nestle) with lactose

Aptamil Pepti

Aptamil Pregomin (plus MCT fatty acids)

Free amino acids

Aptamil Pregomin AS

Neonate infant (Nutritia)

Neonate active (Nutritia)

Neonate advance (Nutritia)

Neonate junior (Nutritia)


6.1.4.6 Pre- and Probiotics


Preventive effects of probiotics are discussed controversially (Rosenfeldt et al. 2003) (see Sect. 5.​9.​6). Possible effects of prebiotic oligosaccharides have been reported in a controlled study (Grüber 2012).

There have been attempts to reduce allergy development by prophylactic intake of probiotics during pregnancy which, however, has not found enough evidence for general recommendation (Isolauri et al. 2000; Kalliomäki et al. 2001).


6.1.4.7 Summary


The longest and scientifically best investigated dietary recommendation for primary allergy prevention consists in exclusive breastfeeding over at least 4 months. Even this recommendation has been controversially discussed in the recent past with regard to atopic dermatitis.

When breastfeeding is not possible, application of hypoallergenic infant formula is recommended; partially hydrolyzed whey preparations as well as extensively hydrolyzed casein products have been shown in large clinical trials to yield the best effects. Eventually, regular intake of fish also as early as during pregnancy and lactation may have beneficial effects as well as a Mediterranean diet and a general diversity of foods. The role of introduction of solid food seems to be less important, and it can be started after the fourth month of life. Recent studies have shown that overweight is associated with a higher risk of asthma; therefore, avoidance of high-calory diets has also been included in recommendations for allergy prevention.


6.2 Secondary Prevention


Secondary prevention describes the detection of risk groups by early screening and the prevention or reduction of developing symptoms. In the case of allergy, this means screening for atopic sensitization and application of preventive measures only in these individuals. The general measures correspond to the above-discussed recommendations for primary prevention.


6.3 Tertiary Prevention: Rehabilitation


Tertiary prevention, also called rehabilitation, is one of the most important strategies in long-term management of allergic patients; it describes all activities after the first diagnosis and treatment in the acute phase in order to achieve as long as possible remission intervals, thus allowing participation in a normal active life in society and occupation. Among the total of rehabilitation costs of most insurance or government agencies, approx. 1–2 % regard allergic skin and airway diseases (Stachow 2002).

In many countries, there are legal conditions for outpatient or inpatient rehabilitation measures which also contain rules for standardization and quality control in the general management of patients with atopic dermatitis. In Central Europe, inpatient facilities specialized in allergic airway and skin diseases are available. In quality control and management programs, studies with regard to quality of life and patient satisfaction as well as days of work loss have been performed. For the indication “atopic dermatitis,” similar to “allergic airway disease,” there was an estimated reduction of costs of around 1000 € already in the first 6 months after an inpatient rehabilitation (Ring et al. 2010).

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Oct 6, 2016 | Posted by in Dermatology | Comments Off on Prevention

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