Determination of allergenicity to three cow''s milk hydrolysates and an amino acid‐derived formula in children with cow''s milk allergy

BACKGROUND: Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed. OBJECTIVE: To determine the tolerance and allergenicity of protein hydrolysate or amino acid-derived formulas in children with IgE-mediated cow's milk allergy. METHODS: Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum-specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum-specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid-derived formula were performed. RESULTS: Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid-derived formula. CONCLUSION: In this study, none of the cow's milk substitutes has been found to be non-allergenic. Our results suggest that in children with IgE-mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid-derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.     

Effect of feeding whey hydrolysate, soy and conventional cow milk formulas on incidence of atopic disease in high risk infants

The effect of feeding different infant formulas on incidence of atopic disease was assessed in a prospective double-blind randomized controlled trial among "high risk" infants with family history of atopy among first-degree relatives. The incidence of atopic eczema, wheezing, rhinitis, gastrointestinal symptoms, and colic was noted and serum IgE antibodies to milk were estimated. Seventy-two infants were recruited into each of the following groups: cow milk whey hydrolysate formula (NAN/HA), conventional cow milk formula (Similac), soy-based formula (Isomil), and exclusive breast feeding for greater than or equal to 4 months. The number of infants who exited for reasons other than atopy and were excluded from analysis were 4, 5, 4, and 12 in the four groups, respectively. The incidence of one or more symptoms of possible allergic etiology was five of 68 infants fed NAN/HA, 24 of 67 infants fed Similac, 25 of 68 infants fed Isomil, and 12 of 60 breast-fed infants. Among symptomatic infants, skin prick test to milk proteins was positive in four out of five infants fed NAN/HA, 16 of 24 fed Similac, 2 of 25 fed Isomil, and 7 of 12 breast-fed. IgE antibodies to milk were found in 2 of 68, 9 of 67, 0 of 68, and 6 of 60 infants in the four groups, respectively. It is concluded that exclusive breast feeding for more than 4 months is partially protective against the development of atopic disease among high risk infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

A hydrolysed rice-based formula is tolerated by children with cow''s milk allergy: a multi-centre study

BACKGROUND: Children allergic to cow's milk are fed a soy- or a hydrolysed cow's milk-based substitute. Neither can rule out a sensitization risk. Previous studies have shown that hydrolysed rice is tolerated by animals and children with multiple food hypersensitivities. OBJECTIVE: A prospective clinical assessment of tolerance to a rice-based hydrolysed formula was carried out in children allergic to cow's milk. Patients and methods One hundred children (42 girls and 58 boys, mean age 3.17+/-2.93 years, median 2.20, range 0.18-14.6 years) with a history of immediate reactions to cow's milk and confirmed at double-blind, placebo-controlled food challenge (DBPCFC) when not contraindicated were assessed for clinical tolerance to cow's milk proteins. Their allergy work-up included skin prick tests with whole milk, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG) and total caseins, and specific IgE determinations using CAP technology were performed against whole milk, ALA, BLG and casein. Sensitization to rice and rice-based hydrolysed formula was similarly investigated. Patients' sera were evaluated at immunoblotting for specific IgE to cow's milk proteins, rice and rice-based hydrolysed formula. DBPCFC was carried out with increasing doses of a rice-based hydrolysed formula. RESULTS: All patients were sensitized to cow's milk and/or at least one cow's milk protein fraction. Eighty-seven out of 99 were positive to cow's milk and/or a cow's milk protein fraction at skin prick test. Positive (>0.35 kUA/L) specific IgE determinations were found for cow's milk and/or milk fractions (92/95), rice (21/91) and hydrolysed rice infant formula (4/91). At immunoblotting, sera from 96 children were positive to alpha-casein (n=54), beta-casein (n=38), ALA (n=57), BLG (n=37) and bovine serum albumin (n=61). Similarly, although patients' sera often contained specific IgE against rice proteins at CAP (21/91) and immunoblotting (70/96), only six very weakly positive responses were observed against rice-based hydrolysed formula. All DBPCFC with rice-based hydrolysed formula were negative. CONCLUSIONS: Rice-based hydrolysed formula is a possible alternative not only for children with multiple allergies, but also for children with cow's milk allergy.     

The patch test, skin prick test, and serum milk‐specific IgE as diagnostic tools in cow's milk allergy in infants

We evaluated the value of the patch test, skin prick test, and milk‐specific IgE by CAP RAST in 301 infants with suspected hypersensitivity to cow's milk. The patch test was carried out with milk powder, and the skin prick test with cow's milk‐based formula. Hypersensitivity to cow's milk was determined with double‐blind, placebo‐controlled challenge. An immediate reaction to cow's milk challenge was observed in 100 infants (33%), a delayed reaction in 76 (25%), and a negative result in 125 (42%). Skin prick test wheals were significantly greater in infants with immediate reactions than in infants with delayed or negative reactions. Milk‐specific IgE was correlated with the skin prick test ( r =0.78, P <0.001, n =268) but did not contribute to further discrimination of immediate reactions from delayed or negative reactions compared to skin prick test alone. In our study population, the skin prick test (diameter ≥3 mm) showed a specificity and sensitivity of 91% and 69%; the results for milk‐specific IgE (≥0.7 kU/l) were 88% and 58%, respectively. The patch test did not distinguish subjects with immediate or delayed reactions from those with negative reactions.     

Effect of a whey hydrolysate prophylaxis of atopic disease.

The incidence of atopic manifestations was analyzed in infants "at risk" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies "at risk" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups.     

Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula

BACKGROUND: Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF). METHODS: Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points. RESULTS: A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months. CONCLUSIONS: Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.     

Higher risk of infantile atopic dermatitis from maternal atopy than from paternal atopy

The risk of infantile atopic dermatitis (AD) posed by maternal atopy and paternal atopy, respectively, were compared in the infants from a birth cohort in whom one of the parents had been designated atopic by skin prick testing. Nineteen with atopic mothers were compared with 20 with atopic fathers. AD, other atopic manifestations and potentially influential factors such as breast-feeding were documented prospectively during the first year in all infants. At 3, 6 and 12 month assessments skin prick sensitivity and total serum IgE concentration were determined. Nine of 19 infants with atopic mothers and two of 20 with atopic fathers had AD (P = 0.023) giving a relative risk of 4.7 (95% confidence interval 2.5 to 9.0). Seven of 19 with atopic mothers and none with atopic fathers had AD with onset before 6 months (P = 0.007). When all types of disease evidence (AD, recurrent wheeze and food reactions) were analysed together no significant difference was apparent between the groups. The two groups were found to be well matched with regard to breast-feeding, time of starting cow's milk, solids and egg, sex, month of birth, parental AD and smoking, race, household pets and neonatal IgE concentration. IgE concentrations at each age and the prevalence of skin prick positivity were similar between the groups. Maternal atopy poses a higher risk for infantile AD and paternal atopy. Whether this may be due to genetic or congenital factors or both is uncertain, but clearly the finding is of relevance in the prediction of allergy in childhood.     

Cow's milk allergy in a patient with hyper-IgE syndrome.

BACKGROUND: Both hyper-IgE syndrome and food allergies can result in the early onset of skin rash, eosinophilia, and markedly elevated serum IgE. Occasionally, it can be difficult to distinguish the 2 disorders. Most patients with hyper-IgE syndrome do not have food allergy. OBJECTIVE: To describe a child with cow's milk allergy associated with hyper-IgE syndrome manifesting as failure to thrive (FTT). METHODS: Epicutaneous skin prick test to cow's milk, CAP radioallergosorbent test, atopy patch tests, and double-blind, placebo-controlled milk challenge (DBPCMC) were performed. RESULTS: During initial presentation at 3 weeks of age, the circulating eosinophil count increased from 13,800/mm3 to 44,254/mm3 within 2 weeks while taking cephalexin. Despite treatment, he had worsening rash and FTT at 10 weeks of age with an IgE level of 8,454 U/mL. After changing from an infant milk formula with whey protein to an amino acid-based formula in combination with oral antibiotic treatment, his rash and growth velocity improved markedly within 2 months. IgE decreased to 2,747 U/mL. He remained clinically well for 12 months. He subsequently developed additional food and inhalant allergies with an increase in IgE to 12,150 U/mL. Cow's milk allergy was confirmed by epicutaneous skin prick test, atopy patch test, and DBPCMC. CONCLUSIONS: Traditional prophylactic antistaphylococcal antibiotics, in combination with Neocate formula, were effective in treating the early skin manifestations of hyper-IgE syndrome and FTT in this infant. Cow's milk protein allergy should be considered in patients with hyper-IgE syndrome and FTT.     

Cow's milk IgE and IgG antibody responses to cow's milk formulas

For comparison of the antigenicity and allergenicity of three cow's milk formulas, serum IgE antibodies to cow's milk, β‐lactoglobulin and casein, and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy. They were participating in a randomized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed (N), a partially hydrolyzed (PH), and a regular cow's milk formula (RM). Only infants who had been formula‐fed for 3 months or more were included. IgE antibodies to cow's milk proteins were more common in the RM group (22/34) than in the N (2/31) and PH groups (3/29). There was a strong correlation between sensitization to cow's milk and β‐lactoglobulin ( r =0.85, P <0.001). The IgG responses to β‐lactoglobulin were low in the N group, intermediate in the PH group, and high in the RM group. High responses, as well as detection of IgE antibodies, were associated with development of atopic disease. The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis. The partial hydrolysate seemed to be less suitable for this purpose.     

Indirect enzyme-linked immunosorbent assay for measurement of human immunoglobulins E and G to purified cow''s milk proteins: application in diagnosis of cow''s milk allergy.

An indirect double-antibody enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human immunoglobulin E (IgE) and IgG to the cow's milk proteins (CMP) alpha-casein, alpha-lactalbumin, and beta-lactoglobulin. Human serum albumin was used as the negative-antigen control. Rabbit anti-human IgE or IgG served as the primary antibody, and horseradish peroxidase-conjugated swine anti-rabbit immunoglobulin served as the secondary antibody. Positive control sera were obtained from patients with well-documented histories of cow's milk allergy, while negative control sera were obtained from cord bloods of healthy full-term infants and from normal adult volunteers without known milk allergy. Test sera were obtained from 41 children (ages, 3 months to 13 years; average age, 2.6 years) with suspected cow's milk allergy and clinical manifestations that included wheezing, rhinitis, atopic dermatitis, urticaria, or gastrointestinal disturbances. The patients were simultaneously evaluated by prick skin testing with scratch test antigen to whole CMP. Although only 13 (32%) of the 41 patients were positive by the prick skin test, 25 (61%) were positive by the IgE ELISA. Of the 25 IgE ELISA-positive patients, 20 were also positive by the IgG ELISA. There was concordance of positive results between skin testing and the IgE ELISA in only 9 patients (22%), and there was concordance of negative results in 12 patients (29%). Discordant results were observed in 20 patients (49%). These results indicate that the ELISA is more sensitive than prick skin testing in the identification of individuals with elevated levels of IgE to CMP.     

No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial

BACKGROUND: Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy. METHODS: We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation. RESULTS: No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA. CONCLUSION: We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.     

Cow's milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE

BACKGROUND: The objective of the present study was to evaluate the relevance of skin tests and the concentration of cow's milk-specific IgE antibodies in correlation with oral cow's milk challenge in infants with suspected cow's milk allergy. METHODS: The study material comprised 143 infants under the age of 2 years who had undergone a diagnostic elimination challenge because of suspected cow's milk allergy in 1996. Cow's milk-specific IgE was measured, and skin prick and patch tests were performed. RESULTS: Of the 143 oral cow's milk challenges performed, 72 (50%) were positive. Of the positive reactions, 22 involved immediate-type reactions. In 50 patients, delayed-onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge-proven cow's milk allergy, 26% showed elevated IgE concentrations to cow's milk, 14% had a positive skin prick test, and 44% had a positive patch test for cow's milk. Interestingly, in most patch test-positive patients, the prick test for cow's milk was negative. CONCLUSIONS: Our study demonstrated that many patients with a negative prick test result had a positive patch test to cow's milk. The patch test was a more sensitive method than the prick test or RAST to detect cow's milk allergy in this study population. Our results indicate that patch testing will significantly increase the probability of early detection of cow's milk allergy. Confirmation of the diagnosis is essential in patients with negative test results but a clinical suspicion of food allergy, and in patch test-positive patients. For this purpose, the most reliable method is the elimination-challenge procedure.     

Immunogenicity and antigenicity of a partially hydrolyzed cow's milk infant formula

We evaluated the immunogenicity and antigenicity of a formula based on partially hydrolyzed cow's milk whey protein in infants at risk of atopy and in controls. Total IgE and specific IgE, IgG, and IgG4 subclass antibodies against egg albumin and cow's milk α-lactalbumin, casein, and β-lactoglobulin were measured by radioimmunoassay of cord blood and of peripheral blood at 5 days and 6 months of life in five groups of infants: 16 breast-fed infants at risk of atopy (group 1), 21 partially hydrolyzed whey formula-fed infants at risk of atopy (group 2), 14 formula-fed infants at risk of atopy (group 3), 10 breast-fed control infants (group 4), and 13 formula-fed control infants (group 5). Total IgE concentration was significantly lower in group 2 at 6 months than in groups 3 and 5 infants and similar to that observed in groups 1 and 4 infants. The concentration of specific antiegg and anti-cow's milk protein IgG and of specific anti-cow's milk α-lactalbumin and β-lactoglobulin IgG4 subclass antibodies was significantly reduced in group 2 as compared to group 3 infants and similar to that found in breastfed infants. In conclusion, the partially hydrolyzed formula was less immunogenic and antigenic than a traditional formula and was as immunogenic and antigenic as breast milk.     

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.     

Milk allergy and vitamin D deficiency rickets: a common disorder associated with an uncommon disease.

BACKGROUND: Cow's milk allergy is one of the most common allergies in infancy. It has an excellent prognosis since most cases resolve by 4 years of age. The complications associated with milk allergy include delayed growth and atopic conditions, such as asthma, allergic rhinitis, atopic dermatitis, and other food allergies. OBJECTIVE: To report a case of vitamin D deficiency rickets in a 2-year-old boy with cow's milk allergy. METHODS: We describe a patient with clinical and biochemical evidence of rickets, including decreased serum calcium, phosphate, and 25-hydroxy vitamin D levels and an elevated alkaline phosphatase level. A dietary history revealed the prolonged absence of dietary vitamin D because the child did not tolerate cow's milk. Skin prick testing and measurement of specific IgE to cow's milk were performed to determine whether there was an allergy to cow's milk. RESULTS: Results of skin prick testing and measurement of specific IgE to cow's milk confirmed an IgE-mediated sensitivity to cow's milk. Introduction of appropriate supplementation into the child's diet resulted in complete resolution of his symptoms. CONCLUSIONS: This case emphasizes that the management of cow's milk allergy involves strict avoidance of the allergenic food while also ensuring that essential dietary requirements are met. A dietary history is crucial at all pediatric visits, and inquiry about supplementation of vitamins and minerals is important, especially in children with food allergies.     

Maintenance of tolerance to cow''s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4

BACKGROUND: The central role of specific IgE in cow's milk allergy (CMA) is well documented. However, less is known about the function of other immunoglobulin isotypes in allergy and tolerance to cow's milk proteins (CMPs). OBJECTIVE: To determine differences in the antibody responses that are associated with allergy and tolerance to cow's milk in allergic, atopic and non-atopic individuals of different age groups. METHODS: Nineteen infants (<1 year), 18 children (6-14 years) and 41 adults (21-68 years) were included. Each age group was comprised of subjects with CMA, atopic individuals without a history of CMA and non-atopic subjects. Levels of specific IgE, IgG4, IgG1 and IgA to whole cow's milk and the six most abundant individual CMPs were determined in plasma by ELISA. For comparison, specific IgE and IgG4 were measured to ovomucoid and house dust mite (HDM) in individuals allergic for the respective allergens, and in atopic and non-atopic subjects without allergy. RESULTS: In infants and children with CMA, alphas1-casein and beta-lactoglobulin induced the highest specific IgE response, whereas alphas1-casein was the most allergenic CMP in adult patients. Specific IgG4 and IgG1 responses were the highest to alphas1-casein and beta-lactoglobulin in all age groups, while kappa-casein and alpha-lactalbumin induced the highest levels of IgA. CMP-specific IgG4 was higher in atopic children and adults without CMA, as compared with non-atopic individuals. A similar difference between tolerant atopic and non-atopic subjects was observed for IgG4 specific to ovomucoid, whereas HDM-specific IgG4 was not detectable in these subjects. CONCLUSION: Maintenance of tolerance to cow's milk in atopic children and adults without CMA is associated with elevated levels of specific IgG4, in combination with low specific IgE. The up-regulation of specific IgG4 in tolerant atopic individuals may be related to the type of allergen and its regular dose of exposure.     

Differences in skin-prick and patch-test reactivity are related to the heterogeneity of atopic eczema in infants

Current data indicate an obvious relation between food allergy and atopic eczema in infants. However, diagnostic methods for food allergy need to be supplemented. The objective was to study the relevance of food patch testing in the detection of food allergy in correlation with oral food challenge and skin prick tests in atopic infants. Infants with atopic eczema (n = 113) aged 2–24 months were studied. Each patient was subjected to double-blind, placebo-controlled, or open cow's milk challenge, and skin prick and patch tests. Polysensitization, as judged from skin test results, was common in patients with atopic eczema (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated with skin prick test positivity and delayed reactions with patch test positivity. Altogether 26% of the cow's milk-allergic infants were detected by patch testing only. Patch testing improved the accuracy of skin testing in the diagnosis of food allergy in infants with atopic eczema, but it needs to be standardized. Polysensitization appears to be more common than generally believed among infants with atopic eczema.     

Tolerance to a rice hydrolysate formula in children allergic to cow''s milk and soy

BACKGROUND: Even hydrolysed cow's milk formulae may retain residual allergens and there are few nutritional options for children with cow's milk allergy (CMA) who also react to soy. OBJECTIVE: To assess clinical tolerance to a rice-based hydrolysate in children with such a clinical presentation. PATIENTS AND METHODS: Eighteen children (six girls and 12 boys; median age 5 years; range 1-9 years) with CMA, who developed clinical reactions to a soy-based formula after 2-18 months' treatment, were recruited between January 1998 and June 1999. Clinical evaluation was by skin prick test (SPT) with cow's milk, casein, lactalbumin, soy and rice allergen extracts, fresh cow's milk, soy and hydrolysated rice formula (HRF). Serology was investigated by CAP system technology and immunoblotting. Assessment of the rice formula was carried out by double-blind, placebo-controlled food challenge with rice hydrolysate. RESULTS: Thirteen children had positive SPT to casein, 10 to lactalbumin, eight to rice and two to rice hydrolysate. Positive serology was found in all patients' sera tested with cow's milk, with soy in 13 sera and with rice in seven. Double-blinded, placebo-controlled challenge with an HRF was negative in all cases. CONCLUSIONS: Children allergic to cow's milk and soy tolerate an HRF clinically. This suggests that rice hydrolysate may be used as a protein source for children with multiple food-induced reactions.     

Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study

The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.