A protocol for oral desensitization in children with IgE-mediated cow's milk allergy

OBJECTIVES: To desensitize children with severe immunoglobulin (Ig)E-mediated cow's milk allergy in a period of 6 months by introducing increasing daily doses of cow's milk (CM) in order to enable the child to assume 200 ml of CM daily, or to induce tolerance of the highest possible CM dose. STUDY DESIGN: Twenty-one children at least 6 years old with severe IgE-mediated CM allergy were admitted to the study. A convincing history of IgE-mediated CM allergy or a positive double-blind placebo-controlled food challenge with CM confirmed the diagnosis. Oral desensitization was performed with increasing doses starting from 0.06 mg of CM proteins. RESULTS: Overall, 15 of 21 children (71.4%) achieved the daily intake of 200 ml during a 6-month period; three of 21 children (14.3%) tolerated 40-80 ml/day of undiluted CM; three of 21 children (14.3%) failed the desensitization because they presented allergic symptoms after ingesting minimal amounts of diluted CM. Conclusions: We successfully desensitized 15 of 21 children with severe IgE-mediated CM allergy in a period of 6 months. We stress the importance of the partial outcome in those three of 21 children who could not reach the maximum amount of 200 ml/day of whole CM, but were able to tolerate 40-80 ml/day of CM. In this way we dramatically reduced the risk of severe reactions after accidental or unnoticed introduction of low quantities of CM. We do not propose generalizing this method beyond trained staff.     

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.     

Skin testing with ultra-heat-treated (UHT) cow's milk in children with cow's milk allergy

BackgroundA large proportion of cow's milk (CM)-allergic children are able to tolerate extensively heated forms of CM such as baked goods. Little is known about whether ultra-heat-treated (UHT) forms of cow's milk are immunologically similar to extensively heated cow's milk and therefore may be tolerated by these children.ObjectiveTo determine whether skin test wheal size using UHT CM was significantly different from other forms of CM and CM extracts.MethodsChildren presenting for oral food challenges with either extensively heated or unheated cow's milk underwent skin prick test (SPT) to commercial CM, UHT CM, evaporated CM, and fresh whole CM. The results were compared between groups of children.ResultsAt study exit, only 14% of children were avoiding all forms of CM, compared with 70% at study entry. No difference was seen in the mean SPT results for UHT CM between those children that could tolerate heated CM compared with those that could not. The mean SPT result for casein was significantly lower in those that could tolerate heated CM. However, within the group of heated milk–tolerant children, the mean SPT for UHT CM was significantly lower than the SPT for fresh whole CM.ConclusionUltra-heat-treated CM does not behave significantly differently from other forms of CM when evaluated by SPT in heated milk–allergic vs heated milk–tolerant children. This suggests that UHT CM is not sufficiently immunologically different from unheated CM to be tolerated by heated CM–tolerant children.     

IgE-mediated allergy to fungal allergens in Finland with special reference to Alternaria alternata and Cladosporium herbarum.

BACKGROUND: Alternaria alternata and Cladosporium herbarum are common fungi in outdoor environments, but their clinical significance has not been elucidated in Finland. OBJECTIVE: To evaluate the prevalence of IgE-mediated allergy and clinical outcomes caused by sensitization to fungal allergens in patients with suspected allergy. METHODS: Skin prick tests (SPTs) were performed with C. herbarum in 6,376 patients and also with A. alternata in 1,504 of these patients. SPTs were repeated in 40 patients who showed a positive reaction to either allergen using commercial and in-house extracts. The association of SPT with allergen-specific IgE antibodies in serum was evaluated. Seven patients also underwent a conjunctival challenge test with these fungal allergens. RESULTS: The prevalence of positive SPT results to A. alternata and C. herbarum was low (2.8% and 2.7%, respectively). Among the 40 patients, atopic eczema/dermatitis syndrome was found in 58%, asthma in 44%, and rhinitis in 31%. Most of the patients displayed SPT reactions also to several other fungal allergens, and 75% to 80% showed a positive SPT reaction to allergens of pet animals or pollens. Four patients had a positive reaction to A. alternata and 6 to C. herbarum in the conjunctival challenge test. CONCLUSION: In the Finnish population with allergic symptoms, IgE-mediated sensitization to 2 common fungal allergens was rare and of minor clinical importance. SPT reactions to fungi are mostly observed in patients with multiple sensitivity to various allergens.     

Natural course of cow's milk allergy in children with atopic dermatitis

Cow's milk is one of the most common food allergens in children with atopic dermatitis (AD). This study was conducted to describe the natural course of cow's milk allergy in children with AD, and to identify factors predictive of outcome. To accomplish this, we reviewed the medical records of 115 children who were diagnosed with AD and cow's milk allergy before 24 months of age to evaluate their clinical characteristics and prognostic factors. During a follow-up period of 24 to 114 months, the median age for tolerance to cow's milk was found to be 67 months. Multivariate analysis using the Cox proportional hazard model revealed that the peak cow's milk-specific IgE level within 24 months after birth was the most important factor for prediction of the outcome of cow's milk allergy. In conclusion, half of the children younger than 24 months of age with AD and cow's milk allergy could tolerate cow's milk at 67 months of age. The peak cow's milk-specific IgE level within the first 24 months of birth is useful to predict the prognosis of cow's milk allergy in children with AD.     

Biochemical markers of bone metabolism in children with cow's milk allergy

Introduction

Patients with cow''s milk allergy (CMA) and following a cow milk protein-free diet for a long time are potentially at risk of developing bone abnormalities. To assess the balance between bone formation and resorption processes, we determined serum concentrations of osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX), fetuin-A, osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in children with CMA.

Material and methods

The study included 50 prepubertal children with diagnosed cow''s milk allergy, who were under systematic medical and nutritional care at the Institute of Mother and Child and 40 healthy counterparts as a control group. The concentrations of bone metabolism markers were determined by immunoenzymatic assays.

Results

The diets of all investigated children were correct in terms of phosphorus and magnesium contents but deficient in terms of calcium and vitamin D. Serum OC and CTX as well as fetuin-A concentrations were similar in both studied groups. The BALP activity was significantly (p < 0.05) higher in children with cow''s milk allergy than in the controls. Serum OPG concentration was comparable in both groups, but the RANKL level was higher (p < 0.05) in CMA children than in healthy ones. Hence, the ratio of OPG/RANKL was lower in children with CMA.

Conclusions

Our study demonstrates slight disturbances in the profile of bone metabolism markers in growing children with CMA. The increase in RANKL level and decrease in OPG/RANKL ratio may contribute to intensification of bone resorption in these patients.     

Paradigm shift in the management of milk and egg allergy: baked milk and egg diet

Heat treatment of several foods, including all types of cooking, has been mainly used to minimize the number of viable microbes, reduce pathogenicity, and destroy the undesirable enzymes, maintaining food quality. In addition, food processing improves sensory, nutritional, and physical properties of the foods, due to food protein denaturation. Heat-induced alterations of food proteins can attenuate allergenicity. In this article, the authors review the important role of thermal processing on milk and egg proteins, which comprise the commonest food allergies in infancy and early childhood.     

Clinical predictors for favorable outcomes in an oral immunotherapy program for IgE-mediated cow's milk allergy

BackgroundAvoidance strategies in patients with cow's milk allergy occasionally fail to protect these patients from inadvertent exposures, leading to life-threatening reactions.ObjectiveTo assess the safety and efficacy of milk oral immunotherapy as an alternative therapeutic strategy.MethodsPatients (n = 280, >4 years old) with IgE-mediated cow's milk allergy were enrolled into a milk oral immunotherapy program at a single hospital center. High-risk patients were not excluded. The treatment protocol consisted of 3 rounds of oral induction performed every 4 weeks. On day 1, a patient's reaction threshold was determined. On days 2 and 3, a tolerated starting dose below the threshold was confirmed. Day 4 mimicked the home treatment, which continued until the next induction.ResultsThe median initial starting dose was 52.5 mg of cow's milk protein. Excluding those whose treatment failed in the first week (n = 5) or are still undergoing treatment (n = 15), 61.5% (160 of 260 patients) achieved 7,200 mg and 85.4% of patients were consuming at least 180 mg of milk protein. Reactions at home requiring the use of injectable epinephrine occurred in 15.7% of patients (44 of 280) and in 0.075% (58 of 77,098) of doses administered. Predictors for achieving a full dose in multivariate analysis included a starting dose higher than 30 mg of milk protein (odds ratio 4.6, P < .001), not requiring epinephrine during induction (odds ratio 5.2, P < .001) or home treatment (odds ratio 2.6, P = .037), and the lack of nonanaphylactic type symptoms (odds ratio 15.6, P < .001).ConclusionMilk oral immunotherapy, carried out in a highly controlled setting, is successful in protecting the overwhelming majority of patients from accidental exposures to cow's milk protein.     

Allergy to goat and sheep milk without allergy to cow's milk

BACKGROUND: Cow's milk (CM) allergy is the most frequent cause of food allergy in infants. Most children who are allergic to CM are also sensitized to whey proteins and/or to the casein fraction and many of them cannot tolerate goat's or sheep's milk (GSM) either. Conversely, the GSM allergies that are not associated with allergic cross-reactivity to CM are rare. METHODS: Twenty-eight children who had severe allergic reactions, including anaphylaxis, after consumption of GSM products but tolerated CM products were recruited in a retrospective study. Whole casein and whey proteins were fractionated from CM and GSM. beta-Lactoglobulin and the different caseins were isolated, purified and used to perform enzyme allergosorbent tests (EAST) and EAST inhibition studies with the sera of the allergic children. RESULTS: Clinical observations, skin prick testing and immunoglobulin (Ig)E-binding studies confirmed the diagnosis of GSM allergy without associated CM allergy. EAST determinations demonstrated that GSM allergy involves the casein fraction and not whey proteins. Cow's milk caseins were not at all or poorly recognized by the patient's IgE, while alphaS(1)-, alphaS(2)- and beta-caseins from GSM were recognized with a high specificity and affinity. In all cases, increasing concentrations of CM caseins failed to inhibit the binding of patient's IgE to sheep or goat milk caseins, whereas this binding was completely inhibited by GSM caseins. CONCLUSIONS: The characteristics of GSM allergy differ from those of the CM allergy because it affects older children and appears later. CM products do not elicit any clinical manifestation in GSM allergic patients, whereas CM allergic patients, usually cross-react to GSM. In all the GSM allergic children, the IgE antibodies recognized the caseins but not the whey proteins. Moreover, IgE specificity and affinity was high to GSM and lower to CM caseins despite their marked sequence homology. Doctors and allergic individuals should be aware that GSM allergy requires a strict avoidance of GSM and milk-derived products because reactions could be severe after ingestion of minimal doses of the offending food.     

Factors that predict the clinical reactivity and tolerance in children with cow's milk allergy

BackgroundSpecific IgE (sIgE) may be used for the diagnosis of cow's milk allergy (CMA) and as a guide to perform food challenge tests in patients with CMA. The effect of genetic variants on the prognosis of food allergy is largely unknown.ObjectiveTo examine the performance of sIgE analysis and the utility of the genetic variants of CD14, STAT6, IL13, IL10, SPINK5, and TSLP in predicting the clinical course in children with CMA.MethodsSerum sIgE levels of 94 children who underwent open food challenges and 54 children with anaphylaxis due to cow's milk (CM) were retrospectively analyzed between January 2002 and May 2009. The genetic polymorphisms were determined in 72 children.ResultsA total of 148 children were followed up for a median of 3.5 years, and 42 of the 94 challenge results were positive. The probability curves with 95% decision points were 2.8 kU/L for younger than 1 year, 11.1 for younger than 2 years, 11.7 for younger than 4 years, and 13.7 for younger than 6 years. Sixty-six children outgrew CMA during follow-up. Children with initial an CM sIgE level less than 6 kU/L outgrew CMA earlier than children with an initial CM sIgE level of 6 kU/L or higher (P < .001). The age of tolerance development for CM was significantly higher in children with the GG genotype at rs324015 of the STAT6 gene compared with those with the AA+AG genotype (2 years [range, 1.5-3.9 years] vs 1.2 years [range, 1.0-2.2 years]) (P = .02).ConclusionThe decision points of sIgE obtained in different age groups may help to determine the likelihood of clinical reactivity more precisely. The results suggest that sIgE levels and STAT6 gene variants may be important determinants to predict longer persistence of CMA.