Prevention and management of food allergy

The phenotypic expression and natural history of food allergy vary widely according to the patient's age, disease presentation and type of offending food. Prevention of food allergy might be achieved by altering the dietary factors responsible for the sensitization and phenotypic expression of the disease. Owing to the peculiarity of the atopic status, a minute amount of allergens can trigger both sensitization and symptoms in atopic individuals. The oral dose of beta-lactoglobulin causing sensitization can be estimated to be between 1 ng and several milligrams. In food allergy, sensitization and treatment are allergen specific; therefore, for primary prevention (avoiding sensitization) and secondary prevention of food allergy (avoiding symptoms in an already sensitized subject), a product without immunogenic and allergenic epitopes should be given in each case. Babies of atopic parents are particularly prone to develop food allergy and for this reason they are called high-risk babies. Cow's milk is the most commonly offending food in both gastrointestinal and cutaneous manifestations. Cow's milk proteins are potent allergens and around 2.5% of infants experience cow's milk allergy in the first years of life. The major risk factors for cow's milk allergy are positive family history of atopy and early exposure to cow's milk proteins. Hydrolysate formulae have been developed for the purpose of reducing the allergenicity of cow's milk proteins. More recently, partially and extensively hydrolysed formulae have also been used for feeding babies with a high risk of atopy for the prevention of cow's milk allergy. However, according to the results of a recent randomized controlled study, only an extensively hydrolysated formula, and not a partially hydrolysated formula, significantly decreased the prevalence of cow's milk allergy.     

Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis

Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulae (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino-acid-based formulae (AA) in such infants. We therefore performed a prospective, controlled, multi-center trial to study the efficacy of AA in comparison with eHF, on the growth and clinical symptoms of 73 infants (median age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's milk allergy/intolerance was proven in all infants by double-blind, placebo-controlled food-challenge. We observed a significant improvement in the SCORAD index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p < 0.0001) after 6 months. In the AA group there was a significant increase in the length standard deviation score (p < 0.04), whilst there was no difference in the eHF group. The weight-for-length values were stable in both groups. The energy intake during the study was similar in both groups. Both an AA and eHF resulted in a significant clinical improvement in infants with an early onset of symptoms of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth compared with feeding eHF, despite similar dietary intakes, and may therefore be considered as a beneficial alternative in infants with severe cow's milk allergy intolerance.     

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.     

Cow's milk allergic patients should be informed of the sources of caseinate

Cow's milk allergy is one of the most common food allergies prevalent during infancy and it may cause anaphylactic reactions in more sensitive patients. Cow's milk is found in a large variety of processed foods but its presence may be hidden as it is occasionally listed on the product label in an manner unrecognizable to the consumer. The parents of more sensitive patients need to be instructed in the detection of these potential sources of hidden cow's milk by judiciously reading food labels and in recognition of the sources, thus avoiding possible untoward reactions. We report a patient with cow's milk allergy who had an anaphylactic reaction following the ingestion of a hot dog product that contained caseinate. The label of the ingested hot dog product listed only the code number of caseinate. Avoidance of such occurrences would be more likely if firstly food products were labeled more accurately and secondly if physicians were to instruct their patients more thoroughly about their allergies, including the relevant names of all allergens.     

水解蛋白婴儿配方研究进展

牛奶过敏足婴幼儿最主要的食物过敏类型,1岁以内婴幼儿大约有2.5%的人群表现牛奶过敏.以天然牛奶蛋白为基础的水解蛋白配方,其变应原性降低,其中部分水解蛋白配方(pHF)可诱导口服免疫耐受,主要用于预防婴儿食物过敏和特应性皮炎;深度水解配方主要用于治疗婴儿牛奶过敏;严重牛奶过敏导致生长发育障碍的患儿,应用氨基酸配方治疗.     

Time course of allergy to extensively hydrolyzed cow's milk proteins in infants

We report on the follow-up of 22 infants allergic to cow's milk proteins who did not tolerate extensively hydrolyzed protein formulas. After successful use of an amino acid-based diet for a duration of 11.8 +/- 8.7 months, evolution differed according to the presence or absence of associated allergy to other foods. Cow's milk protein tolerance occurred earlier in the patients (n = 9) whose allergy was limited to cow's milk proteins and to extensively hydrolyzed protein formulas.     

Dietary prevention of allergic disease in children: Are current recommendations really based on good evidence?

We provide a critical appraisal of the literature on the effects of dietary prevention of atopic disease in children. In our view, currently available studies suffer from lack of blinding which is a major problem if the primary end point is subjective (such as the diagnosis of eczema). In addition, long-term follow-up suggests that atopic symptoms are delayed rather than truly prevented, and that only the mildest cases are prevented (or delayed). Although it has been reported that cow's milk allergy is truly prevented by dietary interventions in early life, this has never been demonstrated by double-blind placebo-controlled food challenges. No studies to date have shown effects of hypoallergenic formulae on objective markers of atopic sensitization, such as specific IgE levels. Finally, there is no universally accepted pathophysiological mechanism which could explain the usefulness of hypoallergenic formulae in allergy prevention. In conclusion, we feel that the currently available evidence on the allergy preventive effects of hypoallergenic formulae is insufficient to justify blanket advice being given to 'high risk' families. Such advice gives parents the hope that they can actually prevent allergy in their children which may not be justified. A cautious approach in advising interventions with hypoallergenic formulae to prevent allergy in high-risk infants is warranted.     

Cow's milk protein intolerance: clinical and pathogenic aspects (author's transl)

Cow's milk protein intolerance is a transient food intolerance of early infancy. Ingestion of cow's milk protein causes an enteropathy of variable degree. Clinical manifestations are primarily gastrointestinal, although dermal and respiratory symptoms add to the clinical syndrome. Three types are found: an acute anaphylactic reaction, a chronic mild form, and a chronic severe form which is of utmost practical importance in severe protracted diarrhoea of infancy. A graduated diagnostic procedure is proposed, taking into account clinical and morphological reactions to cow's milk proteins. Pathogenesis is immunologically mediated. A concept of transient food protein intolerance is developed which has to be separated from the permanent intolerance of gluten in coeliac disease. Prognosis of cow's milk protein intolerance is excellent after elimination of the offending agent. Breast feeding seems to be effective in prevention of the disease.     

A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis

Cow's milk and soy protein allergies are commonly associated with atopic dermatitis (AD) in young children. Amino acid (AA)-based elemental milk formula may improve AD control in these patients. This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status. AD patients younger than 3 yr old were eligible. Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E (IgE) assay. Patients were then randomly allocated to take either active treatment or pre-existing formulae (placebo) for 6 wk. They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk. Fifteen AD patients, with median (interquartile range, IQR) age of 1.4 (0.6-2.6) yr, were recruited. Their median (IQR) SCORAD score was 23.9 (10.5-29.7). Seven of them were sensitized to cow's milk or soybean. Among 11 patients who completed the study, the median changes for all scores and urinary eosinophil protein X (EPX) concentration were not statistically significant. There was also no evidence of carry-over effects for SCORAD and its various components and global health score, except for urinary EPX concentration (p = 0.05). Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status.     

Cow's milk protein allergy through human milk

Cow's milk protein allergy (CMPA) is the first allergy that affects infants. In this population, the incidence rate reaches 7.5%. The multiplicity and aspecificity of the symptoms makes its diagnosis sometimes complicated, especially in the delayed type (gastrointestinal, dermatological, and cutaneous). CMPA symptoms can develop in exclusively breastfed infants with an incidence rate of 0.5%. It, therefore, raises questions about sensitization to cow's milk proteins through breast milk. Transfer of native bovine proteins such as β-lactoglobulin into the breast milk is controversial: some authors have found bovine proteins in human milk but others point to cross-reactivity between human milk proteins and cow's milk proteins. However, it seems that a small percentage of dietary proteins can resist digestion and become potentially allergenic. Moreover, some authors suspect the transfer of some of these dietary proteins from the maternal bloodstream to breast milk, but the mechanisms governing sensitization are still being studied. Theoretically, CMPA diagnosis is based on clinical observations, prick-test or patch-test results, and cow's milk-specific IgE antibody concentration. A positive food challenge test usually confirms the diagnosis. No laboratory test is available to make a certain diagnosis, but the detection of eosinophil cationic protein (ECP) in the mother's milk, for example, seems to be advantageous since it is linked to CMA. Excluding cow's milk from the mother's diet is the only cure when she still wants to breastfeed. Usually, cow's milk proteins are reintroduced after 6 months of exclusion. Indeed, the prognosis for infants is very good: 80% acquire a tolerance before the age of 3 or 4 years. Mothers should not avoid dairy products during pregnancy and breastfeeding as preventive measures against allergy.     

Importance of a particular formula of soybean milk without S2 globulin, in the treatment of allergy to cow's milk proteins

Replacing cow's milk with a soybean milk is one of the first measures which are commonly taken with babies suffering from cow's milk protein allergy. Unfortunately soybean can induce sensitization, too, with a variable percentage (ranging from 12 to 80%) according to the different Authors, due to the presence of allergenic proteins, among which the most important one seems to be S2 globulin. An excellent tolerability has been reported in a study carried out with 20 babies suffering from cow's milk protein allergy besides a good palatability of the product with a solution of symptoms in 87.3% of the cases. Only in 16.7% of the treated babies intolerance has been reported and therefore we can conclude that soybean milk has proved to be an excellent substitute of cow's milk in babies suffering from cow's milk protein allergy.     

Prospective study on the atopy preventive effect of maternal avoidance of milk and eggs during pregnancy and lactation

Abstract The preventive effect of maternal avoidance of cow's milk and eggs on the development of atopic dermatitis and sensitization to food allergens was studied in a prospective trial with families at high risk for atopy. intervention included encouraging exclusive breast feeding for at least 3 months and delaying the controlled introduction of solid foods. In addition, one group received a maternal diet with the complete avoidance of milk and eggs in the last trimester of pregnancy and during the period of exclusive breast feeding, another group had the same diet starting after delivery, and mothers of the third group had no dietary restrictions. The period prevalences of atopic dermatitis as well as the rates of specific sensitization to eggs and milk at 6 and 12 months were not significantly different between groups. We were unable to demonstrate a significant preventive effect of maternal diet.Conclusion While breast feeding should be promoted for children at risk for atopy, mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period.     

Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year

Cow's milk allergy is the most frequent childhood food allergy. Children older than 5 who have not become tolerant have less probabilities of natural tolerance. Specific oral desensitization methods are being investigated in reference centres. The aims of our study were to assess the efficacy of our guideline of specific oral desensitization to cow's milk in children and to know its suitability for anaphylactic children. Both clinical and specific IgE outcomes were evaluated. Eighty-seven children aged 5 to 16?years with a history of cow's milk allergy were included. Prior to desensitization, skin prick test, specific IgE to cow's milk proteins and a double-blind placebo control food challenge were performed in all. Of the 87 patients, 21 had a negative challenge; they were considered tolerant, and they were told to follow a free diet. Of the positive, 44 were anaphylactic and 22 non-anaphylactic. All of them were included. In non-anaphylactic patients, 6 achieved partial and 16 maximum desensitization after 23.1?weeks. In the anaphylactic group, 7 achieved partial and 35 maximum desensitization after 26.4?weeks. Cow's milk-specific IgE levels and casein-specific IgE levels were significantly lower in the tolerant patients at baseline. One year after desensitization, the medium specific cow's milk levels and casein IgE levels had dropped significantly. Conclusions: Our guideline for specific oral desensitization to cow's milk is efficacious even in patients with anaphylactic reactions to cow's milk and represents a significant life change. Immunological changes in 1?year show a drop in cow's milk protein-specific IgE.     

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.     

Formula feeding during cow's milk allergy

Cow's milk allergy (CMA) is an immunologically mediated reaction to cow's milk proteins, which affects infant and young children. Cow milk elimination requires either breast-feeding, with or without elimination diet in mother or the use of specific formulas, based on cow's milk protein extensively hydrolyzed, which fit 90-95% of children with cow's milk allergy. In others, still reactive to allergic remnants in hydrolysates, an amino acid based formula is the optimal option. The good tolerance of soy formulas in a reasonable proportion of children with cow's milk allergy make them useful, including as a 1(st)-choice alternative, except probably for those below the age of 6 months. Any elimination diet in children is at risk of nutritional deficiency so that a constant monitoring of the growth parameters should be kept in those children.     

Dietary prevention of allergic diseases in infants and small children

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light into this issue, a group of experts of the Section of Pediatrics EAACI critically reviewed the existing literature on the subject. In this paper, the immunology of the fetus and newborn is reviewed as well as the post-natal development of the immune system. The influence of post-natal environment and breastfeeding on tolerance induction and sensitization are examined. Allergic diseases result from a strong relationship between genetic and environmental factors. Sensitization to food allergens occurs in the first year of life and cow's milk allergy is the first food allergy to appear in the susceptible infants. Hypoallergenicity of food formulas to be used is a critical issue both for treatment of cow's milk-allergic children and for prevention. Methods to document hypoallergenicity are discussed and evaluated in the preclinical and clinical steps.     

Early sensitisation and development of allergic airway disease - risk factors and predictors

The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first months of life seem to be a particularly vulnerable period and there is evidence that sensitisation is related to the level of allergen exposure during early life. At present, the combination of atopic heredity and elevated cord-blood IgE seems to result in the best predictive discrimination as regards development of allergic disease at birth. Early sensitisation, cow's milk allergy and atopic eczema are predictors for later development of allergic airway disease.Exposure to indoor allergens, especially house dust mite allergens, is a risk factor for sensitisation and development of asthma later in childhood in high-risk infants and infants with early atopic manifestations.     

Could whey be responsible for the development of cow's milk allergy in newborns and infants?

Cow's milk allergy is the most common type of food allergy in infants. Most infants develop symptoms one week after initiating the feeding of cow's milk based formulas though sensitisation in utero and via mother's milk are also possible. We report on three newborns who received whey baths after birth and developed allergic skin reactions. Cow's milk allergy was diagnosed. In our opinion the whey baths could be responsible for the sensitisation via skin and the allergic skin reactions. The risks and benefits of whey baths for newborns and infants should therefore be carefully considered.     

Atopy-suggesting symptoms in the first 2 years of life. Effect of gestational age, nutrition and social class

In a prospective study on 318 non-selected infants signs of atopy as well as interrelations with feeding regimens and family history of atopic disease were investigated at the age of 1 1/2 year. The study population was recruited from preterm and term babies hospitalized 1985 in the University Children's Hospital Freiburg, Germany. The most common symptom was eczema. In addition, clinical symptoms of atopy in first degree relatives were a significant risk factor. Because the highest incidence of atopic symptoms occurred in preterm born children with allergic background in their families, we therefore consider this population at highest risk to develop atopic disease. On the other hand there was no significant influence of breast feeding, cow's milk formula and the time of intake of allergenic food on the clinical manifestation of atopy in any group. Although eczema occurred predominantly in infants with higher social level the respiratory tract symptoms were reported more frequently in children from working class families. We therefore regard the social status as an important confounding variable in the studies of risk factors for the development of allergy.     

Cow's milk allergy: guidelines for the diagnostic evaluation

About 2% of the general population and up to 6% of children suffer from food allergy. Cow's milk is charged with a important role in infancy after weaning, since conventional formula are based on its procession. IgE-mediated and Non-IgE- mediated allergic reactions, which are different in manifestation and pathogenesis, can be distinguished. A special role play the exacerbation of atopic dermatitis and the gastrointestinal-food-hypersensitivity-reactions. Skin-prick-test and determination of specific IgE are important diagnostic tools beside medical history. The golden standard of diagnosis is the double-blind-placebo-controlled-food- challenge. The clear result from food-challenge allows to verify suspected food allergies or, on the other hand, to avoid unnecessary diets. Extensively-hydrolysed-formula or Amino-acidformula are a high nutritional value alternative in case of proved cow's milk allergy in infancy.