P. G. Giampietro

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

Objectives: To desensitize children with severe immunoglobulin (Ig)E‐mediated cows milk allergy in a period of 6 months by introducing increasing daily doses of cows 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.

Allergenicity of goat’s milk in children with cow’s milk allergy

BACKGROUND Cows milk allergy (CMA) is a common disease of infancy and childhood. An appropriate cows 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, goats 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.

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

Cows milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cows milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cows milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cows milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cows milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cows 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 cows 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 cows milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cows milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.

Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy : follow-up at 4 yr and 8 months

Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow‐up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)‐mediated cow’s milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long‐term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4–5 yr were recorded. Children underwent SPT, and end‐point SPT, with casein and α‐lactoalbumin. Specific CM IgE was also measured. At follow‐up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or α‐lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and α‐lactoalbumin (end‐point SPT) significantly decreased after the 6‐month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow‐up. A significant reduction of serum‐specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time‐consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.

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 cows 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 doctors supervision. However, the majority of the SPT‐positive children did tolerate the two extensively hydrolyzed whey‐based formulas tested.

Oral food desensitization in children with IgE-mediated hen's egg allergy: a new protocol with raw hen's egg.

To cite this article: Meglio P, Giampietro PG, Carello R, Gabriele I, Avitabile S, Galli E. Oral food desensitization in children with IgE‐mediated hen’s egg allergy: a new protocol with raw hen’s egg. Pediatr Allergy Immunol 2012: 00.

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.

Soy formulas and nonbovine milk

BACKGROUND Cows milk allergy is frequently observed during the first year of life when nutritional requirements are critical. In those cases where breast-feeding is not available, a safe and adequate substitute to cows milk should be offered. OBJECTIVE The primary aim of this review is to evaluate the clinical use of milk derived from vegetable proteins, such as soy, or from animals such as goat, mare, or donkey, or elemental diet in children with cows milk allergy. METHODS MEDLINE searches were conducted with key words such as soy, goats milk, donkeys milk, mares milk, and elemental diet. Additional articles were identified from references in books or articles. Original research papers and review articles from peer-reviewed journals were chosen. RESULTS Soy formulas are nutritionally adequate and can be used in children with immunoglobulin E-mediated nongastrointestinal manifestations of cows milk allergy. Goats milk is as allergenic as cows milk. Mares milk and donkeys milk may be used in selected cases of cows milk allergy after appropriate modification to make them suitable for human infants. Elemental diets are usually restricted to the most severe cases of cows milk allergy (ie, sensitivity to extensively hydrolyzed protein formulas). CONCLUSIONS Vegetable formulas obtained from soy and milk derived from other mammals, such as mare or donkey, homemade preparations, and elemental diet may represent valid alternatives for children with cows milk allergy. Extensive clinical trials are needed on the safety profile of any alternative mammal-derived milk. The choice of alternative milk should take into account the clinical profile of the child allergic to cows milk, particularly as concerns age, severity of symptoms, degree of sensitivity to cows milk proteins, and any multiple food allergies.

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 cows milk allergy and who had been prospectively followed up, from birth to 5 years.

Soy protein formulas in children: no hormonal effects in long-term feeding.

Recently, the finding of high plasma concentration of phyto-oestrogens in soy protein formula (SPF) fed children has focused scientific attention on the phyto-oestrogens (isoflavones genistein, daidzein, and their glycosides) contained in SPFs. The aim of this study was to evaluate some hormonal and metabolic effects of long-term (more than 6 months) SPF feeding. We enrolled 48 children, mean age 37 months (range 7-96 months), 27 males and 21 females. All children underwent physical examination. Bone age, urinary markers of bone metabolism, serum levels of bone alkaline phosphatase, osteocalcin, 17beta-oestradiol, and intact parathyroid hormone were measured. Eighteen healthy children represented the control group. No abnormalities were observed in auxological parameters; none of the enrolled girls showed signs/symptoms of precocious puberty and none of the boys presented gynecomastia; bone age was within the normal range. The serum level of bone alkaline phosphatase, osteocalcin, 17beta-oestradiol, and intact parathyroid hormone, and the urinary levels of the markers of bone metabolism were all within normal values. We conclude that long-term feeding with SPFs in early life does not seem to produce oestrogen-like hormonal effects.