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.     

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.     

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.     

A prospective study of humoral immune responses to cow milk antigens in the first year of life

Previous studies have shown that in cow milk allergy the specific immune response to dietary cow milk antigens is deficient. This study aimed at delineating the development of humoral immune response to cow milk antigens in healthy infants. Twenty-five healthy newborns were enrolled, and seen at scheduled visits at the ages of three, six and eleven months, and they formed two groups: those breastfed and those fed adapted cow milk formulae. The local immune response in the gut was approximated using the ELISPOT assay of circulating antibody secreting cells. At the age of three months, in the formula fed group, cells secreting specific IgA to cow milk antigens were detected despite low levels of IgA serum antibodies. The total number of IgA secreting cells increased with age (p = 0.001). The milk in the infant diet directly influenced this development so that the age related increase was significantly greater in the formula fed group (p = 0.04). The results indicate that diet has a significant effect on the developing immune system, and that healthy infants are able to respond in an antigen specific fashion to dietary antigens, which may be central in attaining clinical tolerance of such antigens.     

Specific IgE antibodies to cow's milk and individual cow's milk proteins in children with suspected allergy to cow's milk

Specific IgE antibodies against whole-milk-antigen mixture and against casein, alpha-lactalbumin and beta-lactoglobulin were determined using the radioallergosorbent test (RAST) in 125 sera of children with an initial diagnosis of suspected cow milk allergy. The results of the RAST were correlated with the clinical diagnosis. No specific IgE antibodies could be demonstrated in 98 children. Of these, 20 (20%) showed clinically intolerance to cow milk presumably on the basis of other immunological mechanisms. Specific IgE antibodies could be demonstrated in the sera of 27 children. Of these, 16 (60%) actually showed allergy to cow milk. A statistically significant association with chi 2 test could be established between positive RAST and clinical diagnosis (p = 0.001).     

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 of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation

The purpose of this study was to determine whether a new ultrafiltrated whey hydrolysate infant formula, Profylac®, could be administered safely to children with cow milk protein allergy/intolerance. Profylac has a stated molecular weight of < 8 kD and at least 30, 000 times reduced antigenicity which is controlled by a combination of ELISA-techniques and immunochemical methods. The study comprised 66 children with cow milk protein allergy/intolerance diagnosed by controlled elimination/ challenge procedures. The children were aged 1 month-14. 5 years, median 1% years and 15 were below 1 year. Thirty-five of these children had proven IgE-mediated reactions (cow milk protein allergy). Sixty-one of the children had at least two different symptoms and 31 had concomitant allergies to other foods and/or inhalants. All 66 children underwent and tolerated open, controlled challenges with Profylac. A total of 64 children continued having Profylac daily for at least 3 months and 58 for at least 6 months after challenge. Nine of the children older than 1 year did not like the taste and only had Profylac in minor amounts. No side effects were registered. Fifteen of the infants were below 1 year of age, and this group was compared with an age matched group of 16 infants challenged with and fed an extensively hydrolysed casein hydrolysate, Nutramigen®. All the infants in these two groups accepted and tolerated Profylac and Nutramigen, respectively, and no side effects were registered. Among the 35 patients with IgE-mediated reactions 6% (2/35) had positive skin prick tests and 11% (3/28) had specific IgE class 2 against Profylac, 2 of the latter before intake of Profylac. None of the patients with non-IgE-mediated reactions had a positive skin prick test or specific IgE against Profylac. The study provides 95% confidence that this product is tolerated by at least 95% of children with cow milk protein allergy/intolerance and by 90% with IgE-mediated reactions. We conclude, that this ultrafiltrated whey hydrolysate is generally safe to feed to children with verified adverse reactions to cow milk protein, including children with IgE-mediated reactions. The taste of the product was widely accepted, also by older children.     

Ass''s milk in children with atopic dermatitis and cow''s milk allergy: Crossover comparison with goat''s milk

Cow milk allergy is a common disease of infancy, often associated with atopic dermatitis (AD). Avoidance of cow milk (CM) implies the use of alternative dietary supports such as mammalian milks. In this study, we assessed the tolerability and clinical effect of ass's milk (AM), when compared with the largely used goat's milk (GM) in a single-blind, controlled, randomized crossover. Twenty-eight children with AD and ascertained allergy to CM were enrolled. The children were randomized to AM or GM for 6 months, then switched to the other milk for further 3 months. The SCORAD index (SI) and a visual analog scale (VAS) were evaluated blindly. After termination of the study, food challenges with GM and AM were performed. An SDS-PAGE analysis of different milks was performed. Two children from the GM group dropped out after randomization and 26 completed the study. Ass milk invariantly led to a significant improvement of SI and VAS of symptoms (p < 0.03 vs. baseline and inter-group), whereas GM had no measurable clinical effect. At the end of the study 23 of 26 children had a positive food challenge with GM and one of 26 with AM. Ass's milk had a protein profile closer to human milk than GM. Ass milk is better tolerated and more effective than GM in reducing symptoms of AD. It may represent a better substitute of CM than the currently used GM.     

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.     

The response of bovine beta‐lactoglobulin‐specific T‐cell clones to single amino acid substitution of T‐cell core epitope

Cow’s milk is one of the most common food allergens in the first year of life, with approximately 2.5% of infants experiencing an allergic reaction to it. Beta‐lactoglobulin (BLG) is one of the major allergens in cow’s milk. Previously, we reported that four of six T‐cell clones (TCC) which were established from cow’s milk allergy patients recognized BLGp97‐117 as the core sequence and also recognized BLG in association with the human leucocyte antigen (HLA)‐DRB1*0405 allele. Using two of these four TCCs, we evaluated the T‐cell response to BLG peptides with single amino acid substitution or deletion and identified BLGp102‐112 as the minimum essential region in BLGp97‐117. In the alanine‐scan assay, the proliferative responses of TCCs to pE108A disappeared, and the proliferative responses of TCCs to pC106A decreased. In the analog peptide proliferation assay, pY102S had retained some T‐cell response to the two TCCs. Collecting these results, we propose a motif for the interaction between the HLA‐DRB1*0405 allele and antigen peptide, and suggest that BLGp105‐108 are important residues to retain the TCR/BLG‐peptide/HLA complex. pY102A and pY102S are partial agonists for the T‐cell receptor. These peptides might be considered as candidate peptides for the modification of the T‐cell response to BLG in cow’s milk allergy.     

Manifestations of milk allergy in infancy: clinical and immunologic findings

In a study of the manifestations of cow milk allergy in 100 young children (mean age 16 months), 30 items of historical data and information relating to the effects of a standardized milk challenge were entered into a computer data base. Three clusters of patients were derived using a K-means algorithm. In group 1 were 27 patients with predominantly urticarial and angioedematous eruptions, which developed within 45 minutes of ingesting cow milk. They had positive skin test reactions to milk and elevated total and milk specific IgE serum antibody levels. In group 2, 53 patients had pallor, vomiting, or diarrhea between 45 minutes and 20 hours after milk ingestion. These children were relatively IgA deficient. The 20 patients in group 3 had eczematous or bronchitic or diarrheal symptoms; in 17 symptoms developed more than 20 hours after commencing milk ingestion. Of the patients in group 3, only those with eczema had a positive skin test reaction and elevated IgE antibodies to milk. The patients in group 3 were the most difficult to identify clinically; they had a history of chronic ill health, and symptoms developed many hours or days after commencing milk ingestion in the challenge situation. In view of the heterogeneous clinical and immunologic findings in our patients, it is unlikely that a single laboratory test will identify cow milk allergy in all susceptible patients.     

Defective tumor necrosis factor-α production in infants with cow’s milk allergy

As an aid to clarifying the role of immune mechanisms in the development of cow’s milk allergy (CMA) in suckling infants, we studied the capacity of peripheral blood mononuclear cells (PBMC) to produce tumor necrosis factor-α (TNF-α) in vitro. The study population consisted of 43 infants, aged 0.12–11.2 months; of these, 31 had challenge-proven cow’s milk allergy manifested with either skin or gastrointestinal symptoms or both. In addition, 12 healthy infants were studied as controls. The spontaneous, unstimulated and mitogen-induced production of TNF-α and interferon-γ (IFN-γ) by isolated peripheral blood leukocytes was evaluated. TNF-α and IFN-γ production of PBMC was significantly lower in infants with cow’s milk allergy than in healthy children. Our results indicate that, in infants with CMA, the function of TNF-α-producing cells is defective. This might disturb the development of oral tolerance and thereby lead to cow’s milk allergy. These results may help to clarify the etiopathology of CMA.     

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     

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.     

Enhanced levels of cow's milk antibodies in infancy in children who develop type 1 diabetes later in childhood

Background: Early exposure to cow’s milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM‐based infant formula in the trial to reduce insulin‐dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen‐conferred T1D susceptibility and had an affected first‐degree relative. After 7 years of follow‐up, 8 subjects had progressed to T1D, 15 had at least one disease‐associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta‐lactoglobulin (BLG), bovine serum albumin, and alpha‐casein and IgG antibodies to bovine insulin (BI) were measured with enzyme‐linked immunosorbent assays from sequential samples. Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody‐positive subjects than in autoantibody‐negative subjects at 18 months of age (p = 0.022). Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.     

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.     

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.     

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.     

Local immune response in patients with cow milk allergy: follow-up of patients retaining allergy or becoming tolerant.

To assist in identifying factors that determine the clinical outcome of cow milk allergy, we subjected to rechallenge 37 patients with a history of cow milk allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1 months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to assess the total number of immunoglobulin-secreting and specific antibody-secreting cells among peripheral blood lymphocytes primed during provocation by milk antigens, giving indirect evidence of local immune response in the gut. Patients with persistent cow milk allergy (n = 13) had milder reactions at rechallenge than they had shown at the time of diagnosis. Numbers of immunoglobulin-secreting cells in these patients increased significantly from a geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to 2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445 (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of immunoglobulin-secreting cells did not increase during provocation. The total number of IgA-secreting cells before rechallenge was significantly higher than it had been before the initial challenge. The patients who acquired cow milk tolerance also had specific antibody-secreting cells of IgA isotype before the second challenge. These results indicate that in cow milk allergy the ability to mount a local immune response against cow milk antigens, particularly in the IgA class, is related to the suppression of clinical sensitivity.     

Specific oral desensitization in children with IgE-mediated cow's milk allergy. Evolution in one year

Cow's milk allergy is the most frequent childhood food allergy. Children older than 5 who have not become tolerant have less probabilities of natural tolerance. Specific oral desensitization methods are being investigated in reference centres. The aims of our study were to assess the efficacy of our guideline of specific oral desensitization to cow's milk in children and to know its suitability for anaphylactic children. Both clinical and specific IgE outcomes were evaluated. Eighty-seven children aged 5 to 16?years with a history of cow's milk allergy were included. Prior to desensitization, skin prick test, specific IgE to cow's milk proteins and a double-blind placebo control food challenge were performed in all. Of the 87 patients, 21 had a negative challenge; they were considered tolerant, and they were told to follow a free diet. Of the positive, 44 were anaphylactic and 22 non-anaphylactic. All of them were included. In non-anaphylactic patients, 6 achieved partial and 16 maximum desensitization after 23.1?weeks. In the anaphylactic group, 7 achieved partial and 35 maximum desensitization after 26.4?weeks. Cow's milk-specific IgE levels and casein-specific IgE levels were significantly lower in the tolerant patients at baseline. One year after desensitization, the medium specific cow's milk levels and casein IgE levels had dropped significantly. Conclusions: Our guideline for specific oral desensitization to cow's milk is efficacious even in patients with anaphylactic reactions to cow's milk and represents a significant life change. Immunological changes in 1?year show a drop in cow's milk protein-specific IgE.