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.     

Follow-up of children with rhinitis and cough associated with milk allergy

Young children sensitized with foods may develop early respiratory symptoms including nasal symptoms and cough, but not clinical manifestations in the skin or gastrointestinal tract. The long-term outcome of these patients is largely unknown. We studied 36 children sensitized with cow's milk and three different age-matched control groups. The patients were followed from 12 to 18 months of age for at least 5 yr with repeat skin testing and oral food challenge. After 2½ yr, 63.9% (n = 23) of those in the mild allergy group lost sensitivity to foods; after 5 yr, the number was 86.1% (n = 31). However, during the study period of 5 yr, 69.4% (n = 25) simultaneously developed a sensitivity to common indoor airborne allergens. A similar trend was found only in the egg allergy control group. A positive family history and a history of parental smoking significantly increased the relative risk (RR) of sustaining nasal allergy symptoms (RR = 3.33 and 1.79, respectively). We concluded that allergy march from food sensitivity to sensitivity to airborne allergens may occur in a subset of children before 4 yr of age. Genetics and environmental factors might independently contribute to the continuation of these respiratory symptoms.     

Predictive factors for the persistence of cow’s milk allergy

Santos A, Dias A, Pinheiro JA. Predictive factors for the persistence of cow’s milk allergy.
Pediatr Allergy Immunol 2010: 21: 1127–1134.
© 2010 John Wiley & Sons A/S Cow’s milk allergy (CMA) is usually transient, but recent studies have shown a later acquisition of tolerance to CM. Our aims were to characterize a population of Portuguese children with CMA and to identify predictive factors for the persistence of this food allergy. Children with CMA observed in our Paediatric Allergy Clinic between 1997 and 2006 were selected. Demographic and clinical data were collected from medical records. The group of children who tolerated CM before the age of 2 was compared with the group of children who tolerated CM beyond that age or persisted with CMA until the end of the study. Multivariate logistic regression analysis was used to investigate independent predictive factors for the persistence of CMA beyond the age of 2. In the subgroup of children with IgE‐mediated CMA, the acquisition of tolerance was analysed using Cox regression. In this population of 139 children, the majority presented more than one symptom (73%) affecting more than one organ (51%), with cutaneous (81%), gastrointestinal (55%), respiratory (16%) manifestations and/or anaphylaxis (3%). Thirty‐two per cent developed asthma, 20% atopic eczema, 20% rhinoconjunctivitis and 19% other food allergies over time. The acquisition of tolerance was different in the whole population versus the subgroup with IgE‐mediated CMA: 34%versus 0% at the age of 2, 55%versus 22% at the age of 5 and 68%versus 43% at the age of 10. Immediate allergic symptoms, asthma and other food allergies were independent factors for the persistence of CMA beyond the age of 2. Higher maximum weal diameter on skin prick test to CM and higher maximum level of specific IgE to CM were associated with reduced likelihood of acquiring tolerance in the subgroup of children with IgE‐mediated CMA. In conclusion, children with IgE‐mediated CMA acquire tolerance to CM at older age. Clinical parameters and allergy tests may be helpful in defining prognosis. CM‐allergic children tend to develop other atopic conditions and need specialized follow‐up in the long term.     

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.     

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)     

Bone mineral status in children with cow milk allergy

To investigate bone mineral status in children with verified cow milk allergy for more than 4 yr compared with a large reference population of 343 local healthy controls. Whole body bone mineral content (BMC), projected bone area and bone mineral density (BMD) were determined by dual energy x-ray absorptiometry in nine children (8-17 yr old, one girl and eight boys). All children had cow milk allergy for more than 4 yr. All children had asthma and was treated with corticosteroids. BMC and BMD were reduced for age (p < 0.01). Height for age was significantly reduced (p < 0.01), indicating 'short' bones. BMC for bone area was borderline reduced (p = 0.05), indicating reduced bone mineralization. The growth of the children was reduced compared with there parents and siblings (p < 0.01), and the bone age was retarded (mean 1.4 yr, p < 0.01). Calcium consumption calculated from food intake was about 25% of the recommended. All laboratory tests were normal. Short bones were the main reason for reduced BMC and BMD for age in children with cow milk allergy, but a borderline low BMC for bone area indicated reduced bone mineralization of the bones. A supplementation of calcium to children with cow milk allergy is recommended.     

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.     

Milk oral immunotherapy is effective in school‐aged children

Aims: To study the efficacy of oral immunotherapy (OIT) in schoolchildren with cow’s milk (CM) allergy (CMA). Methods: Twenty‐eight children aged 6–14 years with CMA documented by oral challenge were enrolled into a randomized, double‐blind, placebo‐controlled OIT study. In the active treatment, CM protein amount was increased during 23 weeks from 0.06 mg to a maximum of 6400 mg (200 mL of milk). Results: Twenty‐four (86%) patients completed the protocol: 16/18 in active and 8/10 in placebo groups. All children in the active and 2/3 in the placebo group suffered from symptoms considered by the parents as induced by milk. The children were contacted by phone 12 months later, and 13 (81%) used daily CM or milk products corresponding 6400 mg of CM protein. After double‐blind OIT, all 10 children in the placebo group completed successfully an open‐label OIT by an identical protocol, and all used daily CM or milk products 6 months later. Three to 3.5 years later, one child more had discontinued daily milk use. Thus, the long‐term success rate was 22/28 (79%). Conclusions: This placebo‐controlled, double‐blind study confirmed that OIT was effective in desensitizing schoolchildren with CMA. With occasional exceptions, the reached desensitization sustained for more than 3 years.     

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.     

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.     

Association of HLA-DQ7 antigen with cow milk protein allergy in Italian children

In this study we investigated the HLA association with cow milk allergy. Thirty-seven Italian children with cow milk allergy and 35 randomly selected age-matched healthy children as control group were included in the study. DNA typing was performed by restriction fragment length polymorphism (RFLP) technique. We show the first statistically significant positive association between the expression of the HLA-DQ7 antigen and cow milk allergy. Several immunological tests (skin prick test, RIA, radioallergosorb-ent test (RAST) and ELISA) were performed to evaluate the humoral immune responses of DQ7 positive and DQ7 negative allergic patients. Our results show that among the DQ7 positive patients the majority presented a high humoral response. Furthermore, the in vitro proliferative response of patients to the †-lactoglobulin antigen was performed to evaluate their cell-mediated immune response. We observed that the number of the nonre-sponders was higher in the DQ7 positive patients when compared to the DQ7 negative patients.
Our data indicate an association of HLA-DQ7 antigen with cow milk pro tein allergy and that the DQ7 positive patients had a prevalence of humoral rather than cellular responses.     

Diagnosis of IgE‐mediated food allergy among Swiss children with atopic dermatitis

Diagnosis of food allergy in children with atopic dermatitis (AD) relies on a good knowledge of the prevalence of the disease and of the foods most frequently involved. Our objective was to define these characteristics in a population of Swiss children with AD. Patients referred to a pediatric allergist or a dermatologist for AD were routinely tested by skin‐prick test (SPT) to seven common food allergens (milk, egg, peanut, wheat, soy, fish, and nuts), and to all other foods suspected by history. Patients with positive SPTs were further evaluated for specific serum immunoglobulin E (IgE) antibodies (by using the CAP System FEIA^?). CAP values were interpreted following previously published predictive values for clinical reactivity. Patients with inconclusive results (between the 95% negative predictive value [NPV] and the 95% positive predictive value [PPV]) were challenged with the suspected food. A total of 74 children with AD were screened for food allergies. Negative SPTs excluded the diagnosis in 30 subjects. Nineteen patients were diagnosed by histories suggestive of recent anaphylactic reactions to foods and/or CAP values above the 95% PPV. Forty‐three food challenges (35 open challenges and eight double‐blind, placebo‐controlled in children with persistent lesions of AD despite aggressive topical skin treatment) were performed in patients with positive SPTs but with inconclusive CAP values. Six patients were diagnosed as positive to 15 foods. Challenges were not performed to high‐allergenic foods in young children (under 12 months of age for egg and fish, and under 3 years of age for peanuts and nuts). Altogether, 33.8% (25 of 74) of the AD patients were diagnosed with food allergy. The prevalence of food allergy was 27% (seven of 25) in the group referred to the dermatologist for primary care of AD. The foods most frequently incriminated were egg, milk, and peanuts. The prevalence of food allergy in our population was comparable to that in other westernized countries, suggesting an incidence of food allergy in approximately one‐third of children with persistent lesions of AD. Together with milk and eggs, peanuts were most frequently involved in allergic reactions.     

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.     

Feeding a soy formula to children with cow's milk allergy: the development of immunoglobulin E-mediated allergy to soy and peanuts.

Peanut allergy has been associated with the intake of soy milk or a soy formula. We studied the development of immunoglobulin E antibodies specific to soy and peanuts and of allergic reactions caused by peanuts, in children with confirmed cow's milk (CM) allergy fed either a soy formula or an extensively hydrolyzed formula (EHF). One hundred and seventy infants with documented CM allergy (CMA) were randomly assigned to receive either a soy formula or an EHF. The children were followed to the age of 4 yr. Peanut-specific immunoglobulin E was measured at the age of 4. A detailed history of the occurrence of allergic reactions caused by peanuts was recorded by the parents. Soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1, 2 and 4 yr. Immunoglobulin E antibodies to soy (> or =0.35 kU/l) were found in 22 of 70 children fed the soy formula, and in 14 of 70 of the children fed the EHF (p = 0.082). In an open challenge with soy at the age of 4, no immediate reactions were observed. One of 72 children from the soy group had a delayed reaction. immunoglobulin E antibodies to peanuts (> or =0.35 kU/l) were found in 21 of 70 children fed the soy formula and 17 of 69 infants fed the EHF (p = 0.717). The incidence of reported peanut allergy in the soy group was two of 72 (3%) and four of 76 (5%) in the EHF group (p = 0.68). Development of immunoglobulin E-associated allergy to soy and peanuts was rare in our study group of milk allergic children. The use of a soy formula during the first 2 yr of life did not increase the risk of development of peanut-specific immunoglobulin E antibodies or of clinical peanut allergy.     

Macromolecular absorption and cows' milk allergy.

The absorption of macromolecules was analysed by measuring serum concentrations of human alpha-lactalbumin after feeding human milk, using a competitive radioimmunoassay. The control group consisted of 78 children fed by cows'' milk formula; concentrations of alpha-lactalbumin in their serum were low. The median concentrations in the different age groups varied between 7-13 micrograms alpha-lactalbumin/1 serum/1 human milk/kg body weight. Twenty-eight children with cows'' milk allergy were studied before introduction of a diet free of cows'' milk. Nineteen had gastrointestinal and nine skin symptoms. High serum alpha-lactalbumin concentrations were found. Only two children had alpha-lactalbumin concentrations below 100 micrograms alpha-lactalbumin/1 serum/1 human milk/kg body weight. Altogether 76 children on a diet free of cows'' milk were studied directly after a cows'' milk challenge; 26 developed symptoms. They had significantly higher serum alpha-lactalbumin values than the 50 children with no symptoms upon challenge. Eighteen of the 26 children with symptoms had serum alpha-lactalbumin concentrations of more than 100 micrograms/1 serum/1 human milk/kg body weight in contrast with two of the 50 with no symptoms. Total serum IgE antibodies were analysed in 43 children. No correlation was found between concentrations of serum IgE and serum alpha-lactalbumin in the children with cows'' milk allergy.     

A randomized, single-blind and crossover study of an amino acid-based milk formula in treating young children with atopic dermatitis

Cow's milk and soy protein allergies are commonly associated with atopic dermatitis (AD) in young children. Amino acid (AA)-based elemental milk formula may improve AD control in these patients. This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status. AD patients younger than 3 yr old were eligible. Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E (IgE) assay. Patients were then randomly allocated to take either active treatment or pre-existing formulae (placebo) for 6 wk. They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk. Fifteen AD patients, with median (interquartile range, IQR) age of 1.4 (0.6-2.6) yr, were recruited. Their median (IQR) SCORAD score was 23.9 (10.5-29.7). Seven of them were sensitized to cow's milk or soybean. Among 11 patients who completed the study, the median changes for all scores and urinary eosinophil protein X (EPX) concentration were not statistically significant. There was also no evidence of carry-over effects for SCORAD and its various components and global health score, except for urinary EPX concentration (p = 0.05). Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status.     

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.     

Correlation between skin prick test using commercial extract of cow''s milk protein and fresh milk and food challenges

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.     

Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.     

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