Allergenicity of mare's milk in children with cow's milk allergy.

BACKGROUND: Cow's milk allergy is a common disease of infancy and early childhood. If the baby is not breast-fed, a substitute for cow's milk formula is necessary. OBJECTIVE: The aim of this study was to investigate, in vitro and in vivo, the allergenicity of mare's milk in a population of selected children with severe IgE-mediated cow's milk allergy. METHODS: Twenty-five children (17 male and 8 female) aged 19 to 72 months (median age 34 months) with IgE-mediated cow's milk allergy were selected for this study. All the children underwent skin prick tests with cow's milk and mare's milk and double-blind placebo-controlled oral food challenge (DBPCOFC) with fresh cow's milk, fresh mare's milk, and, as placebo, a soy formula (Isomil, Abbott, Campoverde, Italy). We performed immunoblotting of cow's and mare's milk developed with IgE from allergic children. RESULTS: All the children showed strong positive skin test responses to cow's milk (4+); 2 children had positive skin test responses to mare's milk (2+). All children had positive DBPCOFCs to cow's milk; one child had a positive DBPCOFC to mare's milk. No children reacted to the placebo (Isomil). In the cow's milk, some proteins are able to strongly react with human IgE; when the sera are tested with mare's milk, the bands corresponding to the same proteins are recognized by a lower percentage of sera. CONCLUSION: These data suggest that mare's milk can be regarded as a good substitute of cow's milk in most children with severe IgE-mediated cow's milk allergy. It would be prudent, however, to confirm its tolerability by a supervised titrated oral challenge test.

Allergenicity of goat's milk in children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is a common disease of infancy and childhood. An appropriate cow's milk (CM) substitute is necessary for feeding babies with CMA. CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas. In several countries, including Italy, goat's milk (GM) formulas are available, and some physicians recommend them for feeding babies with CMA. OBJECTIVE: We sought to investigate, in vitro and in vivo, the allergenicity of GM in 26 children with proven IgE-mediated CMA. METHODS: All the children underwent skin tests with CM and GM; detection of specific serum IgE to CM and GM; and double-blind, placebo-controlled, oral food challenges (DBPCOFCs) with fresh CM, GM, and, as placebo, a soy formula (Isomil, Abbott, Italy). CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM, respectively. RESULTS: All the children had positive skin test responses and CAP results to both CM and GM, all had positive DBPCOFC results to CM, and 24 of 26 had positive DBPCOFCs to GM. In CAP inhibition tests, preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM. In immunoblotting inhibition assays, preincubation with CM completely extinguished reactivity to GM, whereas GM partially inhibited reactivity to CM. CONCLUSIONS: These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA. A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA.

Natural history of soy allergy and/or intolerance in children, and clinical use of soy-protein formulas.

Atopic diseases of infants and children are common, debilitating, chronic and sometimes even life-threatening. Several well-conducted studies in high risk babies have demonstrated a significant reduction in the prevalence and severity of atopic diseases with dietary and environmental manipulations. The currently available cow's milk (CM) substitutes for infants are soy protein (SP) formulas (SPFs), hydrolyzed formulas (HF), and home-made meat-based formulas. Soybeans have been cultivated in Eastern countries for many centuries and were first used to feed US babies with CM allergy (CMA) in 1929. Since then, SPFs containing purified SP, a mixture of vegetable oils, and purified carbohydrate have been developed. From a nutritional point of view, SPFs are adequate, support normal growth, protein status, bone mineralization, are well accepted, and economical. SPFs are used for different conditions including CMA, lactose and galactose intolerance and in the management of severe gastroenteritis, and some studies show that feeding SPFs for the first six months of life significantly reduces the prevalence of atopic diseases in high risk babies. Although gastrointestinal symptoms and atopic dermatitis (AD) may occur in some SPF-fed children, anaphylaxis following the ingestion of soybean is extremely rare in children. However, in the past few years the antigenicity/allergenicity of SPFs has been over-emphasized in the medical literature. In this paper on the natural history of soy antigenicity/allergenicity we discuss all the pros and cons of SPFs, their composition and nutritional value, the basic immune definitions, chemistry and characterization of SPs. We then discuss the antigenicity and allergenicity of SPFs in animals, recent data on the use of SPFs and the incidence of soy allergy in children, clinical reactions to SPFs, and the clinical relevance of skin testing and IgE antibodies to soy, challenge test procedure, clinical indication of SPFs, and their relevance in the prevention of atopy. We have meta-analyzed 17 different studies and conclude that history-based SPF allergy incidence totals 27%, in skin prick tests (SPT) RAST-oral food challenge (OFC)/double-blind food challenge (DBFC)-based epidemiological studies attains 3%, and in challenge test studies 4%. We suggest that double-blind placebo-controlled food challenge (DBPCFC) studies in larger cohorts of babies may establish a more reliable prevalence of SPF allergy in different disorders associated with CMA.

A three-year prospective study of specific immunotherapy to inhalant allergens: evidence of safety and efficacy in 300 children with allergic asthma.

The effectiveness and safety of specific immunotherapy (SIT) in allergic diseases such as asthma have increasingly come under question. Some authors advocate eliminating SIT as a therapeutic option for allergic patients, since the risks associated with this form of asthma may outweigh its positive effects. However, in a review of twenty-nine controlled studies in 2077 children and an equal number of controls, 27 (93.1%) have shown the effectiveness of SIT in pediatric age for the treatment of asthma due to inhalant allergens (p < 0.0001). The scope of this study was to ascertain whether this form of therapy is safe and effective in pediatrics. 300 children (median age 4.4 years) with asthma due to pollen or house dust mite were prospectively followed for three years. They were randomly divided into two groups: the study group and control group, being almost equal in number of children and clinical characteristics such as sex and age. No child suffered severe reactions due to SIT. Children receiving SIT had significantly greater reductions in days (p = 0.0001) and nights (p = 0.0005) without asthma and drug usage (p = 0.0003), compared with drug-treated children. In addition, the number of asthma attacks (p = 0.0001), and the quality of life were significantly improved in the study group (p = 0.0001). These findings suggest that if suitable allergen extracts are used with close observation of therapeutic indications, and children are followed by their doctors as frequently as required, SIT is effective in the treatment of pediatric asthma, with few adverse effects.

Measles vaccine in egg allergic children: poor immunogenicity of the Edmoston-Zagreb strain.

Despite the fact that a number of recent studies have shown that measles/ mumps/rubella vaccine is safe for egg allergic children, many pediatricians are still concerned about immunization in egg allergic children. In Europe, a measles vaccine with the Edmoston-Zagreb strain (EZMV) grown in human fibroblast culture has been developed and recommended for children with egg allergy. However, some doubt arises on the efficacy of this strain due to its weak immunogenicity. The aim of this study was to investigate the immunogenicity of the EZMV in comparison to the measles vaccine with the Schwarz strain (SWMV) grown in a chick embryo fibroblast culture. Thirty-nine children affected by severe immediate manifestations due to IgE mediated egg allergy were enrolled. The children received at random the SWMV (Morupar, Sclavo) or the EZMV (Triviraten, Berna) in one 0.5 ml subcutaneous injection, and were checked for any immediate allergic reactions in the following 4 hours. Blood samples were taken for the detection of specific antibody response 5 months after the immunization. In SWMV seroconverted children (18/19) the geometric mean antibody titer was 3 times higher than that observed in EZMV seroconverted children (17/20) (p < 0.01). No allergic reactions occurred following the immunization with the two different vaccines. This data confirms the safety of SWMV in egg allergic children. In addition, the present study provides further data on the lower immunogenicity of the EZMV in comparison to the SWMV.

Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study.

The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma.

[The primary and secondary prevention of allergic diseases in the child "at risk" for atopy: a review of the literature and the authors' personal experience]. / Prevenzione primaria e secondaria delle malattie allergiche nel bambino "a rischio" per atopia: revisione della letteratura ed esperienza personale.

The increasing prevalence of the atopic diseases in the industrialized countries is closely linked together the numerous efforts to attempt to prevent them. Several Authors have suggested environmental and/or dietetic measures in the "at risk" babies in the first months of life, more critical for the atopy development. The environmental measures are directed to the avoidance of the major inhalant allergens (house dust mite, pet allergens, cigarette smoking, etc.). The employment of the acaricides can be useful to this purpose. The dietetic measures include: prolonged and exclusive breast feeding in the first six months of life, delayed and gradual weaning, avoidance of the major food allergens (cow's milk proteins, egg, fish, etc.) for the breast-feeding mother, choice of an adequate cow's milk substitute when the breast-feeding is not sufficient. For long time soya milk has been employed. In the last decade partially or highly hydrolyzed formulae were introduced, but in some cases they can be more allergenic of cow's milk. In this paper we reviewed the various environmental and dietetic measures and the different prevention programs that the several Authors have adopted in "at risk" babies.

[Effectiveness of a test for verification of the presence of acari in house dust for the prevention of respiratory allergies in children]. / Efficacia di un test per verificare la presenza degli acari nella polvere domestica nell'ambito della prevenzione dell'allergia respiratoria del bambino.

Respiratory allergy and bronchial asthma in particular can be serious afflictions in younger as well as in older children. Therefore interest has been focused on methods for the prevention of atopy. The role and allergenic importance of Dermatophagoides pteronyssinus (Dpt) in house and other environments have been identified. This mite provokes asthma in children at an earlier age than pollens. However the most under-valued area of asthma prevention is environmental control. The steps may seem difficult at first, but the results will be well worth the efforts and the sacrifices. We report on the high effectiveness of the guanine detection test (Acarex) based on the colorimetric quantification of allergen sources in house dust (mattresses, pillows, upholstered furniture, carpets, moquettes, etc), which can be treated with house dust mite extermination products such as benzyl benzoate. The eradication measures will allow the parents to reduce the allergen exposure, to be monitored at 3-6 month intervals. The guanine detection test performed in our Division on house dust samples assembled by the patents of children with house dust mite induced asthma (study group) or pollen asthma (control group) yielded highly significant statistical differences.

Immunogenicity of a so-called hypoallergenic formula in at-risk babies: two case reports.

The clinical and immunologic findings of two breast-fed babies who experienced anaphylaxis after a feeding with a partially whey hydrolysate formula (PWHF) are reported. Sensitization to this formula seems to have occurred in the first days of life in the Maternity Hospital where the babies were fed the same formula. These two case reports suggest that PWHF may be immunogenic in the IgE system. This data is in agreement with previous studies which showed intact fragments of cow's milk (CM) proteins in PWHF.

Food allergy, atopic dermatitis and superficialism in medicine.

Although the essential immunology underlying atopic diseases is now being clarified, there are still few accountable diagnostic tests. Therefore the recognition and treatment of these diseases continues to be based mainly on clinical skill and, in particular, on the taking of a careful history. This means that the observer bias can be a significant factor, and so whether or not the diagnosis is made may dependent on a clinician's preconceptions. Furthermore, the general interest in the subjects has tended to divided the medical consensus between believers and nonbelievers. In infancy, food allergy has protean manifestations and is provoked by many different food allergens. In addition to the lack of really useful diagnostic tests, there is the difficulty of easily and reliably conducting double-blind challenges in general pediatric practice. Thus it is crucial that a scientific, and critical, approach is adopted and that doctors attentively record the case history and observe the response to elimination diets and challenges. True science has nothing to do with superficialism.

Diagnosis and treatment of food allergy.

There have been significant advances in our understanding of food allergy (FA) in children. The spectrum of food-induced disorders has been defined more clearly, strict criteria for diagnosis have been developed, some understanding of immunopathogenetic mechanisms and the natural history of FA have evolved. In this paper the recent advances are discussed.

[Allergy to cow's milk]. / Allergia al latte vaccino.

Cow's milk allergy is a disease of infancy and usually appears in the first few months of life. The evaluation of infants for possible cow's milk allergy is one of the more common problems encountered by pediatricians. Unfortunately, both over and under diagnosis is frequently seen. In this review the pathophysiology, the clinical manifestations, the diagnosis and management of infants with cow's milk allergy as well as the prevention of the condition in predisposed infants are discussed.

Joubert syndrome. Review of the fifty-three cases so far published.

Joubert's syndrome (JS) is an autosomal recessive disorder, which is characterised by a variable combination of central nervous, respiratory and eye anomalies. We review the clinical characteristics of the 53 so far reported children with Joubert's syndrome, stressing the importance of recognising the syndrome in the neonatal period, in order that specific and effective therapeutic measures be started as soon as possible.