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.     

Prediction of the development of tolerance to milk in children with cow's milk hypersensitivity

OBJECTIVES: To investigate whether the development of tolerance to cow's milk (CM) by aged 4 years can be predicted with a skin prick test (SPT) and measurements of total or specific immunoglobulin E (IgE) in the serum, taken at the time of diagnosis of cow's milk hypersensitivity (CMH). STUDY DESIGN: Infants with immediate (n=95) or delayed (n=67) challenge reactions to CM were prospectively followed to aged 4 years. CMH status was assessed annually by CM challenges. RESULTS: By aged 2, 3, and 4 years, children with delayed reactions developed tolerance to CM faster than those with immediate reactions: 64%, 92%, and 96% versus 31%, 53%, and 63%, respectively. A wheal size of <5 mm in SPT correctly identified 83% of 124 infants who developed tolerance to CM by aged 4 years, and a wheal size of >or=5 mm in SPT correctly identified 71% of 39 infants with persistent CMH. Milk-specific IgE <2 kU/L correctly identified 82% of infants who developed tolerance to CM, and milk-specific IgE >or=2 kU/L correctly identified 71% of infants with persistent CMH. CONCLUSION: SPT and milk-specific IgE in the serum are useful prognostic indicators of the development of tolerance to CM in infants with CMH.     

Selenium content of human milk,cow's milk and cow's milk infant formulas

The selenium content of human milk, cow's milk and cow's milk infant formula were estimated by instrumental neutron activation analysis. The highest values were found in 3 samples of human colostrum (524–865×10^-9 g/g dry weight). There was a significant decrease with increasing time post partum. Mature human milk exhibited a selenium content of 230±79×10^-9 g/g dry weight.The selenium content of 45 samples of cow's milk from the north-western area of Germany was 200±39×10^-9 g/g dry weight. While there was no significant difference between the values of mature human milk and of cow's milk, cow's milk infant formula exhibited significantly (P<0.01) lower values than human milk. The average selenium content of 107 samples of 10 different commercially available fluid and powdered cow's milk infant formulas (range: 18–171×10^-9 g/g dry weight) amounted to about only one third of that in mature human milk.With support of the Deutsche Forschungsgemeinschaft     

Anaphylaxis to sheep's milk cheese in a child unaffected by cow's milk protein allergy

A 5-year-old atopic boy unaffected by cow's milk protein allergy experienced several anaphylactic reactions after eating food containing “pecorino” cheese made from sheep's milk. Prick-prick tests were strongly positive to sheep's buttermilk curd and `pecorino' sheep's cheese. Skin prick tests to fresh sheep's milk and to goat's milk were also positive, whereas they were negative to all cow's milk proteins, to whole pasteurized cow's milk and to cheese made from cow's milk. Specific IgE antibodies were negative to all cow's milk proteins. Conclusion Sheep's milk and cheese derived from sheep's milk may cause severe allergic reactions in children affected and, as we report, in children not affected by cow's milk protein allergy. Received: 14 January 1997 and in revised form: 20 June 1997 / Accepted: 8 July 1997     

An immunocompetent infant with cow's milk allergy and cytomegalovirus colitis

European Journal of Pediatrics - A 5-week-old, severely ill, infant is described with diarrhoea and rectal bleeding, followed by vomiting and dehydration after introduction of a cow's milk...     

Cow's milk protein intolerance and chronic constipation in children

Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3 months to 11 years) with chronic constipation. A diagnosis of constipation was made on the basis of a history of painful elimination of hard stools for at least 1 month, whether or not associated with a reduced frequency of stools or soiling. The children were evaluated using clinical parameters and the following laboratory tests: total serum immunoglobulin E (IgE); specific IgE (radioallergosorbent test [RAST]) for whole cow's milk, α-lactoalbumin, β-lactoglobulin, and a food group; and skin-prick tests with whole milk, α-lactoalbumin, β-lactoglobulin, and casein. Following the evaluation, the children were submitted to a CMP-free diet for a period of 4 weeks. In seven patients (28%), constipation disappeared during the CMP-free diet and reappeared within 48–72 h following challenge with cow's milk. In two infants a rectal biopsy revealed allergic colitis and they therefore did not undergo the challenge. High serum levels of total IgE were observed in five of the children who showed a clinical improvement (71%), a positive skin-test in two (29%), and detectable specific IgE in two (29%). These results suggest that CMP allergy or intolerance should be considered as a cause of chronic refractory constipation in children, although the underlying mechanism still require further investigation.     

Serum total and free tryptophan levels in term infants fed cow's milk formula or human milk

We found no significant differences in mean total and free tryptophan concentrations in sera of healthy, full-term infants fed cow's milk formula and healthy, full-term infants who were breast-fed. Serum tryptophan concentrations were measured 1 h after feeding when the infants were 2 and 6 days of age. In this study cow's milk formula compared favourably with human milk as primary nutrition for full-term infants, despite a two-to-three fold higher level of free tryptophan in human colostrum.     

Cow's milk allergic children can present sensitisation to probiotics

Aim: To evaluate sensitivity to different probiotics in children with cow's milk allergy.
Methods: Eighty-five patients (age range: 4 months –12 years) presenting atopic dermatitis (AD) were enrolled. Skin prick test (SPT) responses to three different probiotics preparations (Fiorilac®, Dicoflor® and Reuterin®) were evaluated in addition to relevant food allergens.
Results: Thirty-nine patients out of 85 (45.8%) had a positive skin response to prick test for cow's milk (3 with reaction <3 mm). Of the thirty-six patients with a cow's milk weal reaction >3 mm, twenty-eight (77.8%) had a skin response to Fiorilac®, four patients (11%) to Dicoflor® and four (11%) to Reuterin®. The proportion of SPT reaction to all the investigated probiotics preparations was significantly lower than cow's milk (r = 9.406; p = 0.002). A significantly higher sensitization was observed for Fiorilac® versus Dicoflor® (r = 30.916; p < 0.001) and versus Reuterin® (r = 34.133; p < 0.001).
Conclusion: Probiotic use in patients with cow's milk allergy has to be limited to products that do not contain milk. This should be clearly reported in the label. In selected patients, it is advisable to perform a screening SPT with the product to evaluate its potential contamination with milk.     

Follow-up of nutritional status and dietary survey in children with cow''s milk allergy

The nutritional status of children with cow's milk allergy was followed during an elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age of two years (range 0.6-4.1 years). The cow's milk allergy had been verified in hospital by a challenge test at a mean age of 0.9 years (range 0.2-1.9 years). Weight, height and laboratory indices to test protein, mineral and vitamin status were measured at three follow-up visits at three-month intervals. In addition to cow's milk allergy all these children had some other food allergies, and six of the 19 children were allergic to soy protein. Only two of the 19 children were given a soy-based formula. In the diets of the other children, cow's milk was replaced by increasing amounts of other foodstuffs and supplementary calcium. At the beginning of the study the relative heights of the children were slightly retarded (-0.6 SD) and remained unchanged during follow-up (-0.8 SD at the end of the study). The relative weights were found to be decreased during follow-up (p less than 0.05). There was a significant reduction in serum prealbumin values; eight of the 19 children showed abnormally low values. Low serum zinc values were seen in 12 children. Serum iron concentration was low in two children and two had high serum alkaline phosphatase values. Seven-day food recording indicated that dietary intake of energy was below the recommendation in some children, but protein intake was high. Some children had low intakes of riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cow's milk protein allergy and gastro-oesophageal reflux

Evidence for cow's milk allergy was looked for prospectively in 15 children with recurrent vomiting. Whereas radiological examination showed gastro-oesophageal reflux to be present in all patients, 3 out of 15 children presented an enteropathy associated with an increased number of IgE plasmocytes in small intestinal biopsy tissue. These three patients did not improve with conventional medical therapy but a striking improvement occurred within 24 h on a cow's milk-free diet. We conclude that diagnostic confusion between gastrooesophageal reflux and cow's milk allergy can occur and that the presence of IgE plasmocytes in small intestinal biopsy tissue indicates IgE-mediated cow's milk protein allergy. All cases of intractable gastro-oesophageal reflux should be suspected of cow's milk allergy and investigated acrodingly.Abbreviation GER gastro-oesophageal reflux     

T-cell signal transduction in children with cow's milk allergy – increased MAP kinase activation in patients with acute symptoms of cow's milk allergy

The precise immune mechanisms behind cow's milk allergy (CMA) are still unknown. Previously, the production of the cytokines TNF-α and IFN-γ in T cells from children with CMA has been shown to be decreased, and the production of IL-4 has been shown to be increased when compared to healthy children. As these aberrations in cytokine production may be associated with disturbances in cellular function, we investigated whether T-cell signal transduction is abnormal in children with CMA. For this purpose we evaluated the activation of the MAP kinase Erk2. Thirty-nine infants were included in the study. Of those with CMA, 13 had acute symptoms and 9 were free of symptoms due to a successful elimination diet at the time of the study. To activate T cells and to stimulate MAP kinase phosphorylation, peripheral blood mononuclear cells (PBMC) were incubated with Concanavalin A (ConA). The change in MAP kinase phosphorylation was measured by Western blotting. The increase in MAP kinase phosphorylation after stimulation with ConA for 5 min was significantly higher in cells from patients with acute symptoms of CMA than in cells from CMA patients free of symptoms or cells from healthy children. A time-course experiment showed that the change in MAP kinase phosphorylation was still increasing after 10 min incubation in cells from patients with acute symptoms of CMA. The increased MAP kinase activation was found to correlate positively with non-IgE mediated CMA in patients with acute symptoms of CMA.     

The role of cow''s milk protein intolerance in steroid-resistant nephrotic syndrome

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested.     

Efficacy of donkey's milk in treating highly problematic cow's milk allergic children: An in vivo and in vitro study

Successful therapy in cow's milk protein allergy rests on completely eliminating cow's milk proteins from the child's diet: it is thus necessary to provide a replacement food. This prospective study investigated tolerance of donkey's milk in a population of 46 selected children with cow's milk protein allergy, for whom it was not possible to use any cow's milk substitute. Thirty-eight children (82.6%) liked and tolerated donkey's milk at the challenge and for the entire duration of follow-up. Catch-up growth was observed in all subjects with growth deficit during cow's milk proteins challenge. The degree of cross-reactivity of immunoglobulin E (IgE) with donkey's milk proteins was very weak and aspecific. Donkey's milk was found to be a valid alternative to both IgE-mediated and non-IgE-mediated cow's milk proteins allergy, including in terms of palatability and weight-height gain.     

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2–4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and / or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.     

Serum immunoglobulin E,IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: Association with prognosis and clinical manifestations

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1–34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk‐specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme‐linked immunosorbent assay (ELISA). The results were compared to those of 30 non‐atopic age‐matched control children. On average, after 9.2 months (range 2–31 months) on a milk‐free diet, a repeated challenge was performed in 38 children. At the re‐challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom‐free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti‐α‐casein IgG level (of 2.10) in children with a positive reaction at the re‐challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re‐challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti‐BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti‐α‐casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.     

High risk of Helicobacter pylori infection associated with cow's milk antibodies in young diabetics

Abstract Antibody titres (IgA and IgG) for Helicobacter pylori were assayed in 69 insulin-dependent diabetes mellitus patients (42 males, age 1–20 years) and 310 healthy controls (171 males, age 1–20 years). A positive antibody titre for Helicobacter pylori was found in 18/69 diabetic subjects compared to 17/310 controls ( p < 0.001). There was no difference between Helicobacter pylori positive and negative diabetic subjects as regards age, sex, duration of diabetes, diabetic control, insulin dose and SDS for weight and height. Gastroduodenoscopy revealed presence of Helicobacter pylori and evidence of gastric inflammation in 7/8 symptomatic diabetic children. There was a significant association in the diabetic subjects between positivity for anti-cow's milk protein and anti- Helicobacter antibodies, compared to the control group. Seven of the 17 diabetics studied within 3 months of the onset of diabetes had positive antibody titres for Helicobacter. Of these seven patients, five were positive for anti-cow's milk protein antibodies. In our study the prevalence of Helicobacter pylori infection was significantly higher in diabetic subjects than in controls, but the infection was asymptomatic and there was no correlation with diabetes control. In diabetic subjects Helicobacter pylori infection was associated with a humoral response to cow's milk proteins and was often present from the onset of diabetes.