Serum Vitamin D levels and Vitamin D supplementation do not correlate with the severity of chronic eczema in children.

BACKGROUND: Eczema is one of the most common chronic inflammatory skin diseases, affecting about 20% of children. The pathogenic mechanisms of eczema are still not fully understood, and current treatment of moderate-severe eczema is often difficult. Recently, it has been suggested that Vitamin D plays a key role in this disease, even if mechanisms are only partially known. OBJECTIVE: The purpose of our study was to assess the 25-Hydroxyvitamin D serum levels in a pediatric population suffering from chronic eczema (IgE-mediated and non-IgE-mediated), and to correlate these phenotypes with the SCORAD severity and selected clinical and biological parameters. Moreover, we aimed to evaluate whether a supplementation of Vitamin D3 could affect the same clinical and laboratory parameters. METHODS: 89 children with chronic eczema were enrolled in the study. Severity of eczema was assessed with the SCORAD index. Past and present history was taken, and patients were divided into two groups according to the state of sensitization. According to a randomization schedule, the enrolled children were assigned to the following groups: supplementation group, which received a daily oral Vitamin D3 supplementation (2000 IUs) for 3 months; control group which received no supplementation. RESULTS: Vitamin D concentrations in patients with moderate and severe eczema were not statistically different from Vitamin D concentration detected in the serum of patients with mild eczema. Furthermore, we did not find any correlation between Vitamin D levels, total IgEs and SCORAD index, both in the Sensitized and in the Not-Sensitized group. The Vitamin D3 supplementation did not influence the SCORAD severity or the total IgEs concentration. CONCLUSION: To our knowledge, our study is the first one that shows no correlation between serum levels of Vitamin D, eczema severity and IgE sensitization in a pediatric population suffering from chronic eczema.

Oral desensitisation with food is food-specific and protein-specific.

The avoidance of food(s) is the main therapeutic approach to food allergy. Nevertheless, orally- or sublingually-administered food allergens have gained attention and a number of food-allergic children can tolerate gradually increasing amounts of cow's milk and hen's egg. Our purpose is to show that oral desensitisation with food is an allergen-specific therapeutic approach and for this, we describe 4 illustrative children with IgE-mediated food allergy. The first was allergic to cow's milk and hen's egg, the second to cow's milk, hen's egg and fish. Both underwent oral desensitisation to both cow's milk and hen's egg. The third child was allergic to cow's milk, hen's egg and fish and underwent oral desensitisation with cow's milk. The last child was allergic to raw but not to cooked/boiled hen's egg and underwent the oral desensitisation with hen's egg. The first 2 children reached the clinical tolerance to cow's milk after the cow's milk oral desensitisation, but reached the hen's egg tolerance only after the hen's egg oral desensitisation. Moreover, the second child did not tolerate fish after being desensitised to both cow's milk and hen's egg. The third child tolerated cow's milk, but not hen's egg and fish, at the end of the cow's milk oral desensitisation. The fourth child could tolerate the previously not tolerated raw hen's egg after the oral desensitisation with raw hen's egg. In conclusion, we indicate that oral desensitisation with food is allergen specific. The induction of the clinical tolerance to one food is not followed by the tolerance to the other food(s) that the patient is allergic to. To obtain a double or multiple food tolerance, separate desensitisation protocols, one for each food, have to be carried out. Oral desensitisation with food discriminates between raw and cooked proteins.

Soy protein for the prevention and treatment of children with cow-milk allergy.

Soy-protein formulas are widely used for feeding babies with cow-milk allergy. When they first were marketed, these formulas were the only available cow-milk substitute and they ensured a normal life for many children who were affected by the large spectrum of clinical manifestations of cow-milk allergy. Soy-protein formulas were also given to allergy-prone infants for the prevention of atopic diseases when breast milk was not available. Several researchers studied the prevalence of soy sensitization in allergic disease. Few studies used a challenge test for the diagnosis of soy allergy, even those in patients in whom soy allergy was suspected. In most studies the diagnosis of soy allergy was based on anecdotal case histories reported by parents and was not substantiated by scientific diagnostic criteria: no challenge test to soy was made nor were data available on specific immunoglobulin E to soy. In this paper we critically reviewed literature on the safety of feeding soy-protein formulas to babies with cow-milk allergy as well as on the prevention of cow-milk allergy.

Is prevention of food allergy worthwhile?

Several studies performed in high-risk babies have demonstrated a significant reduction in the prevalence and severity of atopic diseases with dietary and environmental manipulations. It has been demonstrated that prolonged breast-feeding and the avoidance of cow's milk, eggs and fish during the first three months of lactation significantly decrease both the prevalence and the severity of atopic disease up to the age of 5 years. We have shown a significant reduction in both the prevalence and the incidence of atopic dermatitis, food allergy and asthma in high-risk children followed up to the age of 5 years who received preventive dietary (prolonged breast-feeding, cow's milk- and egg-free diet to the nursing mothers, supplementation with a soya formula containing sucrose when breast milk was not available, delayed weaning) and environmental measures (no smoking and no pets in the house, measures for the elimination of mites, etc.). However, occasionally, breast-fed infants may experience allergic sensitization to food antigens ingested by the mother during lactation. The factors that determine which infants will develop sensitization to food antigens in breast milk are not fully understood. The genetic predisposition to IgE-mediated hypersensitivity reactions is certainly a prerequisite; however, properties of human milk, such as immune characteristics, may play a role in the phenotypic expression of sensitization. Our studies suggest that the abnormally low levels of the long-chain polyunsaturated derivatives found in infants at risk of atopy are unlikely to be corrected by breast-feeding and may explain the contradictory results from studies on the effectiveness of breast milk against the development of atopic dermatitis.

Detection of undegraded beta-lactoglobulins and evaluation of the molecular weight of peptides in hydrolysate cow's milk formulae.

Hydrolysate formulae have been developed with the purpose of reducing the allergenicity of cow's milk proteins, thus providing a suitable formula for feeding babies with cow's milk allergy. More recently, hydrolysate formulae have also been used with babies at high risk of atopy in order to prevent cow's milk allergy. The aim of the present study was to investigate the presence of intact cow's milk proteins and the molecular weights of peptides in several batches of two extensively hydrolyzed formulae and two partially hydrolyzed formulae. The results show the presence of a significant amount of intact beta-lactoglobulin in one partially hydrolyzed formula and of peptides with high molecular weights (>16,900 D) in the two partially hydrolyzed formulae. In conclusion, the present study confirms that partially hydrolysed formulae contain a large proportion of peptides with high molecular weights: in addition, undegraded beta-lactoglobulin was detected in a partially hydrolyzed whey formula. These data strongly indicate that partially hydrolyzed formulae may be not only allergenic in an already sensitized individual, but also immunogenic in a predisposed baby.

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.

[The prevention of allergic diseases in 174 children "at risk" for atopy]. / Prevenzione delle malattie allergiche in 174 bambini "a rischio" per atopia.

Recent studies have demonstrated that it is possible to reduce allergic diseases in subjects "at risk" for atopy through the adoption of particular dietetic-environmental manipulations in the first few months of life. We have followed-up prospectively 174 infants, children and/or brothers of atopics, born at San Giovanni Calibita Hospital of Rome. In all cases, exclusive breast feeding for the first 6 months of life was recommended, with integration/replacement with soy milk (Isomil, Abbott), delayed weaning beyond the 6th month of life and rigorous hygienic environmental manipulation. The low prevalence of atopic disease (10%) and the absence of serious allergic manifestations in this "at risk" population confirms the advantage of such preventive programs.

Immediate reactions following challenge-tests in children with atopic dermatitis.

It has been shown that atopic dermatitis improves in children when certain foods are eliminated from the diet. Because of the unreliability of the history and the low sensibility of the total and specific IgE and skin tests, at present the elimination-provocation test is the most definitive means to establish which are the offending food(s). Although many authors claim that reactions following the challenge test in atopic dermatitis are only of the delayed type, others assert that immediate reactions are frequent and can sometimes threaten life. The pathogenesis of such reactions is not yet completely understood. However, it has been suggested that a direct IgE-mediated mechanism, inducing a release of anaphylactic mediators, could play some role. The aim of our study is to investigate the incidence of immediate reactions which can follow the food challenge in children with atopic dermatitis who have never experienced such reactions and, in addition, to investigate the reliability of total and specific IgE and skin tests in predicting immediate reactions after the challenge test. Our preliminary data indicate that immediate reactions following food challenge are frequent. Moreover they can be severe and cannot be predicted by the history, by the total and specific IgE levels and by the skin tests' results.

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.

Allergenicity and nutritional adequacy of soy protein formulas.

Soy protein formulas are used for different conditions, including cow milk protein allergy, lactose and galactose intolerance, and severe gastroenteritis. Feeding soy protein formulas to normal term infants is associated with normal growth, normal protein nutritional status, and normal bone mineralization. Recent studies of infants fed soy protein formulas exclusively during the first months of life revealed no immunologic abnormality; however, the use of such formulas for management of cow milk protein allergy and for prevention of atopy is controversial. Although in the past decade many studies have stressed soy allergenicity, soy allergenicity has been confirmed by the challenge test in only a few studies. In this article we review the studies dealing with the allergenicity of soy protein formulas. We also present our own data on their use in the prevention and management of cow milk protein allergy.

[Results of a multicentric study for the prevention of atopic allergy. 48 months of follow up]. / Risultati di uno studio multicentrico per la prevenzione dell'atopia. 48 mesi di follow-up.

With the cooperation of 12 Maternity Hospitals we have started a prospective study to evaluate the effect of dietary and environmental measures in the development of atopic disease in "at risk" newborns. The preventive measures included: exclusive breast feeding for the first 6 months of life, soy milk supplement when breast milk is not sufficient, elimination of house dust, no smoking in the house, etc. All infants were seen at the age of 1, 3, 6, 9, 12 months and twice-a-year afterwards. 1213 babies have been enrolled. At the last follow-up of 48 months 531 children are 4 year old. The cumulative prevalence of atopic disease was 20%: 11 (2%) children developed atopic dermatitis, 69 (13%) asthma, 21 (4%) rinithis, 5 (1%) urticaria. The low prevalence of atopic disease and the trivial course of the allergic manifestations in the children who followed the preventive measures (78/444 = 18%) and the higher (28/87 = 32%) in these who did not (p < 0.01) stressed the importance of such manipulations for the prevention of atopy in "at risk" babies.

A protocol for oral desensitization in children with IgE-mediated cow's milk allergy.

OBJECTIVES: To desensitize children with severe immunoglobulin (Ig)E-mediated cow's milk allergy in a period of 6 months by introducing increasing daily doses of cow's milk (CM) in order to enable the child to assume 200 ml of CM daily, or to induce tolerance of the highest possible CM dose. STUDY DESIGN: Twenty-one children at least 6 years old with severe IgE-mediated CM allergy were admitted to the study. A convincing history of IgE-mediated CM allergy or a positive double-blind placebo-controlled food challenge with CM confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.06 mg of CM proteins. RESULTS: Overall, 15 of 21 children (71.4%) achieved the daily intake of 200 ml during a 6-month period; three of 21 children (14.3%) tolerated 40-80 ml/day of undiluted CM; three of 21 children (14.3%) failed the desensitization because they presented allergic symptoms after ingesting minimal amounts of diluted CM. CONCLUSIONS: We successfully desensitized 15 of 21 children with severe IgE-mediated CM allergy in a period of 6 months. We stress the importance of the partial outcome in those three of 21 children who could not reach the maximum amount of 200 ml/day of whole CM, but were able to tolerate 40-80 ml/day of CM. In this way we dramatically reduced the risk of severe reactions after accidental or unnoticed introduction of low quantities of CM. We do not propose generalizing this method beyond trained staff.

Soy hypersensitivity in children with food allergy.

To evaluate humoral (IgE antibodies) and clinical (positive challenge test) soy hypersensitivity prevalence, we studied 317 children (271 boys and 100 girls) with a median age of 5 months (range 1-120) who visited the Division of Allergy and Clinical Immunology of the Pediatric Department of the University of Roma "La Sapienza" because of histories and symptoms suggestive of food allergy. Atopic dermatitis (AD) was present in 247/317 children (78%), diarrhea in 19 (6%), urticaria in 22 (7%), and rhinitis and/or asthma in 29 (9%). All children underwent diagnostic procedures including family and personal history, physical examination, PRIST, and RAST to cows milk (CM), egg, wheat, soy, and Dermatophagoides pteronyssinus (Dpt). Open challenge tests to soy were performed in the hospital under observation and with emergency equipment at hand. The prevalence of humoral sensitization to CM was 54%, to egg 46%, to Dpt 35%, to wheat 24%, and to soy 22%. Only five children had IgE only to soy; six to soy and egg; and 58 to soy, CM, and egg. Only ten children (3%) had positive challenge to soy and only five of them had IgE to soy. RAST had a sensitivity of 0.69, a specificity of 0.83, a negative predictive value of 0.77, and a positive predictive value of only 0.06.

Hypoallergenicity of an extensively hydrolyzed whey formula.

Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.

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.

Anaphylactic reactions to a cow's milk whey protein hydrolysate (Alfa-Ré, Nestlé) in infants with cow's milk allergy.

It has been shown in an animal model that cow's milk (CM) protein hydrolysates do not elicit an antibody response to CM proteins and do not induce passive cutaneous anaphylaxis. In addition, babies fed with these formulae during the first months of life do not show antibodies to betalactoglobulin (BLG). These data suggest that these hydrolysates are not antigenic, therefore they have been employed as CM substitutes for the management of infants with CM allergy (CMA). We report five exclusively breast fed infants aged 3 to 8 months (median age = 5 mo) with IgE-mediated CMA, who experienced allergic reactions when they were first fed (median age = 5 months) with a small amount of CM whey protein hydrolysate (Alfa-Ré, Nestlé). Family history was positive for atopy in 3/5 babies. All infants had atopic dermatitis during breastfeeding, positive skin tests, and RAST to CM proteins as well as to Alfa-Ré. Total IgE levels ranged from 45 to 2,990 U/mL. These data show that Alfa-Ré, a CM whey protein trypsin hydrolysate, can trigger severe allergic reactions in children with CMA and it should be employed with great caution as a CM substitute in the management of CMA.

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.

Soy allergy is not common in atopic children: a multicenter study.

The aim of the present study was to evaluate the prevalence of soy allergy (positive skin test and positive challenge test) in a large cohort of atopic children, many of them soy fed early in life for several months. In order to investigate the prevalence of soy allergy, two groups of children were enrolled into the study. The first group comprised a cohort of 505 children with personal history suggestive of food allergy. The second group included 243 children born of atopic parents, who had been soy protein formula fed for the first six months of life for the prevention of cow's milk allergy and who had been prospectively followed up, from birth to 5 years. As regards the prevalence of soy allergy in the cohort of children suffering from allergic disease: 31/505 children (6%) had positive skin prick test to soy, however only six of the 31 children with positive skin prick test to soy had positive challenge test to soy. With regard to the prevalence of soy allergy in the children who had been soy protein formula fed in the first six months of life (second group): 14/243 children (6%) had positive skin prick test to soy, but the double blind placebo control oral food challenge to soy was positive in only one of these 14 children. In conclusion documented soy allergy is not common in atopic children.