Preventive effect of feeding high-risk infants a casein hydrolysate formula or an ultrafiltrated whey hydrolysate formula. A prospective, randomized, comparative clinical study

In a prospective study of a 1-year birth cohort of 158 high-risk infants the effect of feeding breastmilk, a casein hydrolysate (Nutramigen®) or a new ultrafiltrated whey hydrolysate (Profylac®) on the development of cow milk protein allergy/intolerance (CMPA/CMPI) was assessed and compared. All the infants had biparental or severe single atopic predisposition, the latter combined with cord blood IgE ≥ 0. 5 kU/L. At birth all infants were randomized to Nutramigen or Profylac, which was used when breastfeeding was insufficient or not possible during the first 6 months of life. During the same period this regimen was combined with avoidance of solid foods and cow milk protein. All mothers had unrestricted diets and were encouraged to do breastfeeding only. Moreover, avoidance of daily exposure to tobacco smoking, furred pets and dust-collecting materials in the the bedroom was advised. The infants were followed prospectively from birth to 18 months of age. All possible atopic symptoms were registered and controlled elimination/challenge studies were performed when symptoms suggested CMPA/CMPI. A total of 154 (97%) were followed up and 141 followed the diet strictly. Eighty-eight (62%) of the infants were breastfed for at least 6 months, 20 (14%) were breastfed exclusively, 59 and 62 had varying amounts of Nutramigen or Profylac respectively. CMPA/CMPI was diagnosed in 1/20, 1/59 and 3/62 in the breastfed, the Nutramigen and Profylac groups respectively, but 1 of the latter also had Nutramigen. None of the infants showed reactions against Nutramigen or Profylac. In 4 infants symptoms were provoked by breastmilk when the mother ingested cow milk and in 1 only by cow milk. The incidence of CMPA/CMPI among the infants who followed the dietary prevention programme was 3. 6% (5/141) which was a significant reduction compared to 20% (15/75) in an identically defined high-risk group without dietary preventive measures. None of the infants in the prevention group developed CMPA/CMPI after the age of 6 months. We conclude that feeding breastmilk, an extensively hydrolysed casein formula (Nutramigen) or an ultrafiltrated whey hydrolysate (Profylac) combined with avoidance of solid foods during the first 6 months of life in high-risk infants significantly reduced the cumulative incidence of CMPA/CMPI during the first 18 months of life. No difference was noted whether the infants were fed breastmilk, Nutramigen or Profylac and a diet period of 6 months seems sufficient. Both formulae were well tolerated and accepted by the infants.     

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.     

Serum specific-IgE antibodies to peptides detected in a casein hydrolysate formula

Up to 2. 59% of infants are affected by cow milk hypersensitivity in the first two years of life, although most of these children will "outgrow" their reactivity within 2-3 years. Extensively hydrolyzed ("hypoallergenic") cow milk-based formulae are often recommended as a substitute formula and are generally well tolerated. However, a small minority of cow milk-allergic children experience allergic reactions to the hypoallergenic formulae as well. Utilizing inhibition-ELISAs and sera from patients with IgE-mediated cow milk allergy, we have identified residual protein fractions less than 20 kD in several of the extensively hydrolyzed cow milk-based formulae. Although many of the cow milk allergic children had positive skin prick lests [SPT] to one of the hydrolysate formulae (Nutramigen^ma), the positive skin test result generally did not correlate with clinical reactivity, although the negative predictive value of the negative SPT was excellent. Children with IgE-mediated cow milk allergy and a positive skin prick test to the hypoallergenic formula should probably receive their first dose of the formula in a medical setting so that appropriate therapy can be administered in the unlikely event of an allergic reaction.     

Antigenicity and allergenicity of cow milk hydrolysates intended for infant feeding

Allergenicity and antigenicity of various commercially available cow milk hydrolysates intended for infant feeding were analysed in 45 children with cow milk allergy. The hydrolysates included the whey hydrolysates Beba HA® (Good Start HA®) and Profylac®, and the casein hydrolysates Alimentum® and Nutramigen®. Positive skin prick tests were recorded against Beba HA in 10 of 41 tested children (24%), against Profylac® in 5/34 (15%) and in one each (2.5%) against Alimentum and Nutramigen. Double-blind placebo-controlled oral challenge tests were performed in 11 children with cow milk allergy using Alimentum, cow milk (positive control) and their regular well-tolerated formula (Nutramigen or soy) used as negative control. One child reacted to Alimentum. This patient was the only one with circulating antibodies against the product, as indicated by a positive RAST. High density SDS-PAGE electrophoresis showed that Beba HA contained a number of unresolved proteins, and non-degraded or partially degraded whey proteins in the range of 5–20 kD. Profylac contained strongly stained protein material in the low molecular weight region 1–10 kD. No protein bands could be identified in the casein-based hydrolysates. Residual antigenicity was tested by measuring the content of betalactoglobulin in the hydrolysates. Three of the hydrolysates contained < 0.06 μg/g dry weight, while the concentration in Beba HA was 200 μg/g dry weight. Positive RAST against Beba HA was detected in 11/45 sera (24%) compared to 7–13% against the other hydrolysates. RAST inhibition with the hydrolysates using cow milk discs was very low for all of them. Using dot immuno-binding assay a weak IgE binding with Alimentum was detected in 4 sera, Beba HA and Profylac in each 2 sera and with Nutramigen in one. The data taken together show that all 4 tested hydrolysates retain some allergenicity. There were differences between the products, one of the whey hydrolysates being substantially more allergenic and antigenic than the other tested formulas. The casein hydrolysate Alimentum showed few reactions in vivo and in vitro in this selected group of children but one child reacted when challenged with Alimentum, indicating that there is a risk for general reactions when using any hydrolysed product in subjects allergic to cow milk.     

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.     

The pendulum between food protein-induced enterocolitis syndrome and IgE-mediated milk allergy

The transition from milk protein-induced enterocolitis syndrome to IgE-mediated milk allergy is uncommon. Herein, we describe three infants that suffered from recurrent vomiting and restlessness in response to cow's milk formula with negative skin prick to milk and therefore diagnosed as milk protein-induced enterocolitis syndrome. After recovering and reintroducing cow's milk formula, they developed disseminated urticaria and positive skin prick test to cow milk compatible with IgE-mediated milk allergy. CONCLUSION: An infant that recovers from cow milk food-induced enterocolitis syndrome might develop afterward IgE-mediated cow milk allergy.     

In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae

AIM: Because allergen-reduced formulae are widely used in the prevention and treatment of cow's milk allergy in children and because anaphylactic reactions have been reported for some hydrolysed formulae, it is of clinical relevance to know about the residual allergenicity of so-called hypoallergenic formulae. METHOD: We therefore studied the reactions of 20 children (mean age 1.6 years) with proven cow's milk allergy to a variety of formulae, using skin prick test, specific IgE in serum, protein content and RAST inhibition. RESULTS: Whereas all but two children with a clinically relevant cow's milk allergy had a positive skin prick test to cow's milk, some children still showed positive responses to the partially hydrolysed formulae. No child had a positive skin test to the amino acid formula. Specific IgE to the partially hydrolysed whey formula (median 0.28 U/ml) was significantly lower (p < 0.003) than to cow's milk. Specific IgE to the partially hydrolysed whey/casein formula, soy/pork collagen hydrolysate and the amino acid formula was in a low range (median values 0.19, 0.23 and 0.21 U/ml, respectively). While determination of the protein content of the formulae gave no valid information, RAST/EAST inhibition was highest for cow's milk, followed by the partially hydrolysed whey formula, partially hydrolysed whey/casein formula, soy/pork collagen formula, and the amino acid formula. CONCLUSION: Skin prick test and RAST inhibition test are suitable methods for determining the residual allergenicity of hydrolysed infant formulae, while determination of protein content using the applied modified Lowry method is not helpful.     

Whey protein hydrolysate formula for infants with gastrointestinal intolerance to cow milk and soy protein in infant formulas

Twenty-one infants less than 6 months of age with gastrointestinal symptoms of cow milk and/or soy protein-based infant formula intolerance (diarrhea in 14, hematochezia in 16, emesis in 8, failure to thrive in 4, and colic in 10) were treated clinically with a whey protein hydrolysate formula. Six patients improved when placed directly on the formula, and 15 remained asymptomatic or improved when given the whey hydrolysate formula following initial treatment with a casein hydrolysate or elemental formula. Eighteen had supporting evidence of an allergic basis for their symptoms, including a family history of allergies in 6, a clinical challenge with the offending formula in 1, laboratory tests consistent with atopy in 11, and/or rectal biopsy with histologic allergic features in 7. The whey hydrolysate formula may be an acceptable alternative to soy or casein hydrolysate formulas in most infants with gastrointestinal symptoms of cow milk and/or formula intolerance.     

L'allergie aux hydrolysats de protéines du lait de vache. À propos de huit cas

BACKGROUND: The use of extensively hydrolyzed protein formulas is the best alternative for children with cow's milk allergy, though cases of allergies to hydrolyzed proteins have been reported. The aim of this study was to clarify from our experience the diagnostic, evolutive and therapeutic aspects of allergies to extensively hydrolyzed protein formulas. PATIENTS AND METHODS: We report eight cases of allergy to extensively hydrolyzed protein formulas seen between 1985 and 1998. The diagnostic criteria for allergy were either the appearance of immediate anaphylactic reactions after the ingestion of protein hydrolysate or a positive challenge test with the protein hydrolysate. RESULTS: Four children developed immediate anaphylactic symptoms after ingesting protein hydrolysate, and four children demonstrated subacute or chronic gastrointestinal symptoms. All children who developed acute anaphylactic symptoms had positive skin tests and specific IgF, antibodies (RAST) to cow's milk and/or hydrolyzed proteins. Conversely, in the four children with chronic gastrointestinal symptoms, skin tests and specific IgE antibodies were negative in three cases, but intestinal histology was abnormal in all of them when they were fed with a protein hydrolysate; this became normal after excluding the hydrolysate (data available in only two cases). Three children tolerated another protein hydrolysate form (whey vs. casein), four children had a favourable outcome when fed with human milk, and an amino-acid-based formula was successfully used in the most recent case. Nonhydrolyzed cow's milk proteins were tolerated after the age of 18 months in six children. Other atopic symptoms were observed in six children. CONCLUSION: Allergy to cow's milk protein hydrolysate is rare. The diagnosis is usually easy in children who develop acute anaphylactic symptoms, though intestinal histology is generally necessary for the diagnosis of allergy with chronic gastrointestinal symptoms. Treatment is based on the use of either another protein hydrolysate form (whey vs. casein) or an amino-acid-based formula.     

Skin prick test predictive value on the outcome of a first known egg exposure in milk-allergic children

Children with milk allergy have higher incidence of other food allergies, especially egg allergy. The objective of this study was to ascertain the accuracy of the prick test in children with IgE-mediated milk allergy for diagnosing egg allergy. Children under the age of 1 yr who came consecutively to Allergy Department 2003–05, and were diagnosed with IgE-mediated milk allergy were selected for this study. Egg introduction was completely avoided until the age of 14 months when clinical history, skin prick tests (SPT), specific-IgE antibodies determination and egg challenge test were performed. One hundred and four milk-allergic children were included. At least one positive prick test to any egg allergen was found in 65 out of the 104 (62.5%). Thirty-eight (36.5%) were allergic to egg proteins as well. Prick tests with egg white and ovomucoid (OVM) had the best diagnostic performances showing the largest areas under the receiver operating characteristic curve. The optimal diagnosis cut-off point was 6 mm for egg white and 5 mm for OVM. The positive likelihood ratios for these cut-off points were: 2.95 (95% CI: 1.74–4.99) for egg white prick test, and 20 (95% CI: 2.9–143.7) for OVM prick test. Children with specific IgE-mediated cow's milk allergy must be closely followed as a risk group for egg allergy. Early diagnosis is necessary and the SPT has shown itself to be a very useful tool for diagnosing immediate IgE reactions to egg on first known exposure.     

Hypersensitivity reaction in an infant fed hydrolyzed lactalbumin contained in a semielemental formula

Following introduction of milk protein formula feedings, a 6-month-old male developed profuse, watery diarrhea progressing to shock, requiring cardiopulmonary resuscitation. Reinstitution of enteral feedings with a formula containing hydrolyzed lactalbumin (Travasorb STD) resulted in recurrence of diarrhea with fever. Intestinal and rectal biopsies showed only nonspecific inflammatory changes. He was discharged on an elemental formula (Vivonex). Twenty-three months later, while admitted for evaluation of hypophosphatemic rickets, immunologic testing using the lymphocyte migration inhibition factor (LIF) test demonstrated positive reactions, especially to alpha-lactalbumin (56% inhibition) and whole cow's milk (22%, normal of less than 20% inhibition). Skin tests revealed sensitivity to cow's milk and eggs. Soy formula also produced diarrhea and bloody stools. Protein hydrolysate formulas, touted as hypoallergenic diets, are useful in infants with intolerance to milk protein. This is the first documented case of an immunological reaction to the hydrolyzed whey protein, lactalbumin. Although protein hydrolysate formulas are effective treatment in most infants with milk protein intolerance, allergic reactions are possible. Caution and close observation should be exercised in immunologically sensitized infants rechallenged with any formula.     

Protein hydrolysates: hypoallergenic milks and extensively hydrolyzed formulas. Immuno-allergic basis for their use in prevention and treatment of milk allergy]

Allergy to milk has an estimated incidence of 2.5%. Hypoallergenic milks are partial hydrolysates of proteins with lactose. Extensive hydrolysates of casein are mainly small peptides and do not include lactose in their formula. A primary allergenicity as well as a cross-sensitivity are shown for all partial hydrolysates. Even extensive hydrolysates have a weak potential of cross-allergy. The prevention of cow's milk allergy in infants at peculiar risk, born from atopic parents, is based on breast-feeding and/or partial or extensive hydrolysates. There is no conclusive evidence for the usefulness of eviction of dairy products during pregnancy or during the period of breast-feeding. The treatment needs exclusively extensive casein hydrolysates ensuring a 90% protection with 95% confidence intervals. Predictive prick tests in certain cases may help the choice of another hydrolysate. Severe cases with failure to thrive or multiple food intolerance require an amino-acid based formula (Neocate). A rational diversification of the diet is advised in order to prevent the onset of a multiple food intolerance syndrome which could avert from the recovery of cow milk allergy.     

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Food allergy and atopic dermatitis in infancy: an epidemiologic study

Atopic dermatitis is common in infancy. The role of food allergy in atopic dermatitis of infancy is unclear. We examined the relationship between atopic dermatitis and immunoglobulin E (IgE)-mediated food allergy in infancy. A birth cohort of 620 infants with a family history of eczema, asthma, hayfever or immediate food allergy in a parent or sibling: 487 children had complete data including skin prick tests (SPTs) to evaluate IgE-mediated food allergy to cow milk, egg and peanut. Participants were grouped as no atopic dermatitis (Gp 0) or in quartiles of increasing severity of atopic dermatitis (Gps 1-4) quantified by days of topical steroid use as reported monthly. Adverse reactions to foods were recorded. The cumulative prevalence of atopic dermatitis was 28.9% to 12 months (10.3% of the cohort of moderate severity). As atopic dermatitis severity increased so did the prevalence of IgE-mediated food allergy (Gp 0, 40/346 vs. Gp 1, 6/36 vs. Gp 2, 8/35 vs. Gp 3, 12/35 vs. Gp 4, 24/35; chi(2) = 76; p < 10(-6)), and the frequency of reported adverse food allergy reactions (Gp 0, 43/346 vs. Gp 1, 4/36 vs. Gp 2, 8/35, vs. Gp 3, 5/35, vs. Gp 4, 13/35; chi(2) = 17; p = 0.002). The relative risk of an infant with atopic dermatitis having IgE-mediated food allergy is 5.9 for the most severely affected group. Atopic dermatitis is common in infancy. There is a strong association between IgE-mediated food allergy and atopic dermatitis in this age group.     

Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with DHA and ARA

Nutramigen AA is an amino acid-based formula for infants with multiple food protein intolerance or severe cow's milk allergy. Similar growth, tolerance, and safety profiles were found in a study comparing Nutramigen AA with a control formula (Nutramigen LIPIL) in healthy, term, formula-fed infants in a randomised study. Moreover, no allergic reactions were observed in a double-blind, placebo-controlled food challenge in infants or children randomised to receive Nutramigen AA or placebo (Neocate). In conclusion, Nutramigen AA sustains growth and is well tolerated in babies with cow's milk allergy.     

Food allergies in early childhood. 1. General concepts, etiopathogenesis, and main clinical features

Abnormal immune reactions to food antigens are a rather common event during infancy. Adverse reactions to milk proteins occur in 2.5% of suckling infants. Both IgE and non IgE-mediated allergic mechanisms may be involved in the pathogenesis of food allergy. IgE mediated allergic responses are the most dramatic and the most often diagnosed types. Non IgE mediated food allergy is usually more difficult to diagnose and its clinical course is more chronic. Food induced allergic reactions mediate a variety of symptoms, involving the gastrointestinal and respiratory tract and the skin. A limited number of foods are responsible for the vast majority of allergic reactions: cow milk proteins, egg, fish and peanuts are the main causes. The vast majority of infants with formula-protein intolerance will outgrow their symptoms by the third year of age. Eliminating the food allergens is the only means of dealing with the problem. In part I of this series, immunopathogenic mechanisms and clinical disorders are described.     

Adverse reactions to milk in infants

AIM: To study the age when symptoms of adverse reactions to milk occur, in premature and term children, the debut of various symptoms, immunoglobulin E (IgE)- and non-IgE-mediated reactions and the frequency of tolerance at 1 year. METHODS: Six hundred and eight children, 193 premature and 416 term infants, were followed. Symptomatic children were invited to a clinical examination. The criteria for the diagnosis were: histories of suspected cow's milk allergy (CMA) and proven IgE-mediated reactions to cow's milk or positive elimination/challenge tests. RESULTS: Twenty-seven out of 555 (4.9%) were diagnosed with adverse reactions to cow's milk. All had symptoms before 6 months of age. The main symptoms were: pain behaviour (13), gastrointestinal symptoms (7), respiratory symptoms, (6) and atopic dermatitis (1). One child had proven IgE to cow's milk. Premature and term infants displayed the same symptoms and age of debut. Thirteen children were tolerant to cow's milk at 1 year. CONCLUSION: Adverse reactions to milk start early in life, with pain behaviour, gastrointestinal, and respiratory symptoms being the most common, and rarely atopic dermatitis. Non-IgE-mediated reactions were the most frequent. Symptoms and age of debut were the same in premature and term infants. Half of the children tolerated cow's milk at age 1.     

Comment utiliser le Diallertest® ?

Cow's milk allergy in children may involve several immunological mechanisms, IgE-mediated, responsible for immediate reactions, and non IgE-mediated, responsible for delayed or semi-delayed reactions. Clinical symptoms in children are largely dominated by atopic dermatitis and digestive manifestations, most of the time related to non IgE-mediated reactions, so that classical allergologic investigations, prick tests and measurement of serum specific IgE, are often negative. In these situations dominated by delayed or semi-delayed manifestations of milk allergy, atopy patch tests such as Diallertest^®, a ready-to-use one, may facilitate the diagnosis.     

Value of the histamine liberation test in the diagnosis of intestinal protein intolerance

The validity of the histamine releasing test for the diagnosis of cow's milk, soy, and egg protein allergy was checked in 31 infants with clinical features of intestinal protein intolerance. The test was positive in 12 of the infants, but in only 5 resp. 1 among them the prick or the Ouchterlony test were pathological. The remaining 19 infants reacted negatively in all 3 tests and subsequently tolerated oral protein loading. The results indicate the superiority of the histamine releasing test in comparison to the conventional prick- and Ouchterlony test.     

Lessons from the clinical course of IgE-mediated cow milk allergy in Israel

Cow milk and milk products are the most common food products consumed in Israel; rates of allergy to cow milk exceed those of peanuts in infants and children. The aim of the present study was to evaluate retrospectively the clinical features and natural course of immunoglobulin (Ig) E-mediated cow milk allergy (CMA) in Israel. Data of children diagnosed with CMA from 1995 to 2003, were collected regarding age at first and most recent reactions, symptoms and signs, family history of atopy, other allergic diseases, emergency department visits, hospitalizations, and treatment. Patients with transient CMA were compared to those with persistent CMA (> or =3 yr old). The study group consisted of 105 patients, 43 with transient CMA (age range: 0.48-11 yr). The remaining 62 patients (age range: 3-16.5 yr) did not achieve tolerance to cow milk during the follow-up period. No differences were found between the groups in mean age and symptoms and signs at the first allergic reaction and family history of atopy. Patients with persistent CMA had a higher rate of asthma than patients with transient CMA (61.2% vs. 18.6%, p < 0.001). Fifty patients with persistent CMA had 137 subsequent allergic reactions after diagnosis, 25% of the reactions were due to oral milk challenge at the clinic and 75% due to accidental exposure, of which 13% required an emergency department visit and 8%, hospitalization. Only 19% of the reactions were treated with epinephrine injection. In conclusion, in our experience, less than half of the children diagnosed with IgE-mediated CMA during 9 yr, outgrew it. The patients with persistent CMA have a higher prevalence of asthma compared with the general population or to children with transient CMA. The high number of recurrent allergic reactions due to accidental exposure and the low rate of epinephrine usage in these patients point to a need for better education of patients and their families.