Milk Allergy In Children Research Articles

Clinical Presentations of IgE-Mediated Cow’s Milk Allergy in Children and Factors Affecting the Development of Tolerance

Clinical Presentations of IgE-Mediated Cow’s Milk Allergy in Children and Factors Affecting the Development of Tolerance

The role of online symptom questionnaires to support the diagnosis of cow's milk allergy in children for healthcare professionals - A Delphi consensus study.

Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Cow's milk allergy in children impacts parental or caregiver calcium intake

Food allergies have become a global epidemic, affecting more than 10% of the population and 8% of children worldwide. Eliminating or limiting a food group from the diet can adversely impact micronutrient consumption. Milk allergies can impact the amount of calcium consumed in the diet, serving as a barrier to meeting daily calcium needs. Previous research evaluates the nutritional impact food allergies may have on children diagnosed with food allergies; however, there is a marked gap in literature that investigates the impact that children's allergy may have on their parent or caregiver. We hypothesized that milk elimination in a child's diet resulting from a milk allergy is associated with inadequate calcium intake among parents. Study participants (n=55) lived in the United States and included parents or caregivers of a child with a diagnosed milk allergy (experimental group) and parents of a child without a milk allergy (control group). Calcium intake was estimated by using the validated Calcium Assessment Tool. Results demonstrated that the experimental group consumed significantly less calcium (273 mg/d) than the control group (520 mg/d; P < .01). Notably, both groups consumed inadequate calcium relative to the calcium Recommended Dietary Allowance for adults of 1000 mg/d, although calcium supplementation was not assessed in this study. Key findings from this study indicate widespread inadequate dietary calcium intake and suggest a need for increased calcium consumption in this population.

Oral immunotherapy for Immunoglobulin E-mediated cow's milk allergy in children: A systematic review and meta analysis.

BackgoundCow's milk allergy (CMA) is the most common allergy in infants that decreases the quality of life of patients and their families. Standard treatment for CMA is the strict avoidance of milk; new treatment strategies such as oral immunotherapy (OIT) have been sought for patients with CMA. We aimed to assess the clinical efficacy and safety of OIT in the treatment of children with immunoglobulin E‐mediated CMA (IMCMA).MethodsWe searched all randomized controlled trials in which OIT is used to treat children with IMCMA from five international electronic databases. We estimated a pooled risk ratio (RR) for each outcome using a Mantel–Haenzel fixed‐effects model if statistical heterogeneity was low.ResultsEleven studies were chosen for meta‐analysis, including a total of 469 children (242 OITs, 227 controls). One hundred and seventy‐six patients (72.7%) in the OIT were desensitized compared with 49 patients (21.6%) in the control group (RR: 7.35, 95% confidence interval (CI): 2.82–19.13, p < .0001). The desensitization effect of OIT was particularly significant in children over 3 years old (RR: 18.05, 95% CI: 6.48–50.26, p < .00001). Although adverse effects were common, they usually involved mild reactions, but epinephrine use was more common in the OIT group (RR: 7.69, 95% CI: 2.16–27.33, p < .002).ConclusionOIT can lead to desensitization in the majority of individuals with IMCMA, especially in patients over 3 years old. A major problem of OIT is the frequency of adverse events, although most are mild. OIT may be an alternative treatment in the future.

Detection and management of milk allergy: Delphi consensus study.

There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.

Discrepancy between Guidelines and Clinical Practice in the Management of Cow’s Milk Allergy in Children: An Online Cross-Sectional Survey of Polish Physicians

The aim of this study was to assess the compliance between current guidelines on the diagnosis and management of children with cow’s milk allergy (CMA) and clinical practice by a survey of Polish physicians. An online cross-sectional survey involving a convenience series of participants was performed from January 15 to March 20, 2020. Data provided by 605 physicians (74.2% of them pediatricians working in general practice) were analyzed. Contrary to the current recommendations, only a minority of respondents (27.4%) reported performing oral food challenge (OFC) to confirm the diagnosis of CMA. Among those who reported performing OFC (n = 160 respondents), the majority performed an open challenge (82.5%). Most respondents (79.2%) correctly recommended as the first-line treatment extensively hydrolyzed cow’s milk formula for a child with mild-to-moderate CMA. Less than half of participants (43.8%) recommended amino acid-based formula for a child with severe CMA (anaphylaxis). Only half of respondents (50.8%) reassessed tolerance to cow’s milk proteins. For assessing tolerance acquisition, more respondents recommended challenge to baked milk compared with fresh cow’s milk (60.5% vs. 39.5%, respectively). This survey study found that only a minority of responding physicians follow current guidelines for diagnosis and management of children with CMA in Poland.

Investigation of Basophil Activation Test for Diagnosing Milk and Egg Allergy in Younger Children.

In children with concomitant food allergy and atopic dermatitis (AD), uncovering the causative food allergen is more arduous. We evaluated the basophil activation test (BAT) for its diagnostic value in children, including those with AD, for milk or egg allergy. We simultaneously measured serum-specific immunoglobulin E (sIgE) levels and performed BATs for cow’s milk and egg white. We compared their overall diagnostic performance using the area under the receiver operating characteristic curve (AUC) with the Delong method and compared them in children with AD. Analyses were completed for 75 children for milk allergy and for 85 children for egg allergy. The sIgE and percentage of basophils with the expression of CD63 were correlated for both milk (r = 0.384, p < 0.001) and egg (r = 0.557, p < 0.001). The AUC of sIgE (0.701) for milk allergy was significantly increased when combined with the BAT (0.805; p = 0.029). In children with AD, the AUC of the BAT (0.924) for milk allergy was significantly larger than that of sIgE (0.701; p = 0.017). The BAT is a potentially useful diagnostic tool for milk allergy in children when combined with sIgE. Moreover, it may be a surrogate marker for milk allergy in children with AD.

Detection of Metabolite Biomarkers for the Early Diagnosis and Prognosis of Cow's Milk Allergy in Children

Detection of Metabolite Biomarkers for the Early Diagnosis and Prognosis of Cow's Milk Allergy in Children

Influence of Atopic Dermatitis on Cow's Milk Allergy in Children.

Background and Objectives: Cow’s milk protein allergy (CMA) is the most common allergy in children. The natural history of CMA is generally favorable and the majority of children reach tolerance during childhood, even if studies show variable results. Atopic dermatitis (AD) is a complex disease from an immunological point of view. It is characterized by an impaired skin barrier function and is often the first clinical manifestation of the so-called “atopic march”. The aim of our study is to evaluate, in a cohort of children with CMA, if the presence of AD in the first months of life can influence the atopic status of patients, the tolerance acquisition to cow’s milk, the level of specific IgE (sIgE), and the sensitization towards food and/or inhalant allergens. Materials and Methods: We enrolled 100 children with a diagnosis of CMA referred to our Pediatric Allergology Unit, aged 1–24 months at the time of the first visit. Results: 71 children had AD and 29 did not. The mean follow-up was 5.28 years. The CMA manifestations were mainly cutaneous, especially in children with AD (91.6% vs. 51.7%; P < 0.001). Patients with AD showed higher rates of polysensitization to foods and higher levels of both total IgE and sIgE for milk, casein, wheat, peanuts, and cat dander at different ages when compared to patients without AD. We analyzed the presence of IgE sensitization for the main foods and inhalants at various ages in the two groups of patients: a statistically significant difference emerged in the two groups of patients for milk, yolk and egg white, hazelnut, peanuts, soybean, grass pollen and cat dander. Meanwhile, we did not find significant differences in terms of tolerance acquisition toward cow’s milk, which was nonetheless reached around 5 years of age in 61% of patients. The level of cow’s milk sIgE at the age of 5 years was significantly higher in the group of patients who did not acquire tolerance (38.38 vs. 5.22 kU/L; P < 0.0001). Conclusions: An early barrier deficiency appears to promote the development of allergic sensitization, but does not seem to influence the acquisition of tolerance.

Adverse Events in Oral Immunotherapy for the Desensitization of Cow's Milk Allergy in Children: A Randomized Controlled Trial

This study focuses on the side effects of cow's milk oral immunotherapy (CM-OIT) using consensus definitions of food-induced anaphylaxis. To evaluate the risk of allergic reactions (ARs) and to identify risk factors associated with higher risk of anaphylactic ARs (AARs) during CM-OIT in children. Clinical charts of children receiving CM-OIT were carefully reviewed. ARs were defined as single-organ ARs, and AARs were defined as involvement of 2 organ systems and/or hypotension in response to CM protein. Descriptive statistics were used to represent demographics, occurrence, reaction characteristics, and comorbidities. Poisson analysis was performed to evaluate risk factors associated with AARs. Among 41 children undergoing CM-OIT, 11 discontinued the treatment (N= 26.8%). The mean age at challenge was 12.1 years (standard deviation [SD], 3.6) and half were male (56.1%). The mean number of AARs per patient was 6.0 (SD, 3.5) versus a mean of 17.4 (SD, 11.9) non-AARs per patient. Among withdrawals from OIT, the mean number of AARs per patient was 8.3 versus 5.1 in nonwithdrawals. AARs were more frequent in children with higher specific IgE (sIgE) for α-lactalbumine and casein at baseline (1.11 [95% confidence interval (CI): 1.01, 1.22] and 1.01 [1.0, 1.03], respectively). Children with resolved eczema and higher sIgE for β-lactoglobuline at baseline (0.13 [95% CI: 0.04, 0.46] and 0.96 [95% CI: 0.94, 0.99], respectively) were less likely to develop AARs. Although the majority of ARs during OIT are nonanaphylactic, AARs occur frequently. Children with higher sIgE for α-lactalbumine and casein at baseline seem to be at higher risk for AARs during OIT.

The Basophil Activation Test reduces the need for a food challenge test in children suspected of IgE‐mediated cow's milk allergy

The gold standard for the diagnosis of cow's milk allergy is the Double-Blind Placebo-Controlled Food Challenge (DBPCFC) test. However, disadvantages of the DBPCFC are the potential risk of anaphylactic reactions, the time-consuming procedure and high costs. The aim of this study was to determine the reliability of the Basophil Activation Test (BAT) both for the initial diagnosis of cow's milk allergy in children and for the determination of tolerance in children with cow's milk allergy. Ninety-seven BATs and cow's milk-specific IgE (sIgE) tests were performed in 86 infants/young children, suspected of (persistent) cow's milk allergy, who were qualified for an in-hospital DBPCFC. The BAT was performed with cow's milk extract and the purified major allergens casein, α-lactalbumin, β-lactoglubulin. Basophil activation was determined by CD63 upregulation measured by flow cytometry. The BAT results were compared to the DBPCFC outcomes. Based on unequivocal DBPCFC and BAT result combinations (80%), the BAT had a sensitivity and specificity of 100% (CI: 86%-100% and 68%-100%, respectively) in IgE-sensitized children (41% of the tested children). All non-IgE-sensitized children (59%) had a negative DBPCFC and BAT, except for five patients. These latter showed delayed and relatively mild symptoms in the DBPCFC with a negative BAT, supporting a non-IgE-mediated allergy in these children. The BAT seems reliable and cost-effective to diagnose patients with an IgE-mediated cow's milk allergy. In IgE-sensitized patients, a BAT might replace a DBPCFC. For non-IgE-sensitized patients presenting with mild symptoms, we propose to consider a (double-blind) extended (time) challenge test at home.

The protective effect of milk consumption on milk allergy in children and adults in Fez-Meknes region of Morocco

PurposeThe purpose of this study is to compare the evolution of self-reported milk allergy in children and adults within the population of Fez-Meknes region, as well as to investigate the consumption of milk and its correlation to milk allergy.Design/methodology/approachIt is a cross-sectional study conducted in Fez-Meknes region between April 2014 and March 2015 basing on a questionnaire completed by 3,068 children and 1,281 adults.FindingsThe results showed that food allergy was more reported among children (29.4 per cent) than adults (16.9 per cent). Milk allergy was reported by 5.3 per cent of children and 4.2 per cent of adults. Children reported mostly cutaneous manifestations (64.8 per cent) while adults reported mostly gastrointestinal manifestations (68.5 per cent). The consumption of milk showed a protective effect against the development of milk allergy (p < 0.001).Originality/valueThe consumption of milk was associated significantly with a low rate of milk allergy, especially in adults. However, the pasteurization of milk seemed to be correlated to increase milk sensitivity.

Early risk factors for cow's milk allergy in children in the first year of life.

Background: Cow's milk allergy (CMA) is a key form of food allergy (FA). It was shown that the frequency of FA seems to have increased during the past 10-20 years, which led to the thought that FA may have different risk factors. Epigenetic regulations and environmental pre- and postnatal factors play a large role in contributing to allergy. Understanding the risk factors that pertain to the development of FA may help to provide reasonable recommendations for prevention of the disease. Objective: To assess the impact of perinatal and environmental risk factors on the incidence of CMA in children in the first year of life. Methods: The study group consisted of 138 infants with CMA and 101 healthy infants without allergy. CMA was confirmed by an elimination test and oral food challenge. To assess infant, parental, and environmental risk factors, we used a validated questionnaire survey. Results: The incidence of CMA was three times higher in infants with a positive family history for allergy (p < 0.001). An analysis revealed that mothers of children with CMA were fourfold more frequently university educated than mothers of children without allergy (p < 0.0001). The ages of the mothers from the study group were significantly higher than the ages of the mothers from the control group. Children from the study group were breast-fed for a significantly shorter time than children from the control group. The risk of CMA was threefold lower in children who had pets at home (p = 0.0002). The risk of IgE-mediated CMA was twofold higher than the risk of non-IgE-mediated CMA if the family had more children (p = 0.04) and as many as ninefold higher if multiorgan symptoms were detected (p = 0.01). Conclusion: A positive family history of allergy and mother's education increased the risk of CMA in children in the first year of life, whereas having pets at home and a longer period of breast-feeding decreased the risk.

Partially hydrolyzed whey proteins prevent clinical symptoms in a cow's milk allergy mouse model and enhance regulatory T and B cell frequencies.

Partially hydrolyzed cow's milk proteins are used to prevent cow's milk allergy in children. Here we studied the immunomodulatory mechanisms of partial cow's milk hydrolysates in vivo. Mice were sensitized with whey or partially hydrolyzed whey using cholera toxin. Whey-specific IgE levels were measured to determine sensitization and immune cell populations from spleen, mesenteric lymph nodes and Peyer's patches after oral whey administration were measured by flowcytometry. Whey-specific IgE and IgG1 levels in partial whey hydrolysate sensitized animals were enhanced, but challenge did not induce clinical symptoms. This immunomodulatory effect of partial whey hydrolysate was associated with increased regulatory B and T cells in the spleen, together with a prevention of IgM-IgA class switching in the mesenteric lymph nodes and an increased Th1 and activated Th17 in the Peyer's patches. Partial hydrolysate sensitization did not induce whey-induced clinical symptoms, even though sensitization was established. Increased regulatory cell populations in the systemic immune system and a prevention of increased total Th1 and activated Th17 in the intestinal immune organs could contribute to the suppression of allergic symptoms. This knowledge is important for a better understanding of the beneficial effects of hydrolysates.

Why whey? Camel whey protein as a new dietary approach to the management of free radicals and for the treatment of different health disorders.

The balance between free radicals and antioxidants is an important factor for maintaining health and slowing disease progression. The use of antioxidants, particularly natural antioxidants, has become an important strategy for dealing with this cause of widespread diseases. Natural antioxidants have been used as therapeutic tools against many diseases because they are safe, effective, and inexpensive and are among the most commonly used adjuvants in the treatment of several diseases. Camel whey protein (CWP) is considered a strong natural antioxidant because it decreases oxidative stress, enhances immune system function, and increases glutathione levels. The structure of CWP is very similar to that of other types of whey protein from different types of milk. CWP contains many components, such as lactoferrin (LF), lactalbumin, lactoglobulins, lactoperoxidase, and lysozyme, and is rich in immunoglobulins. However, in contrast to other WPs, CWP lacks β-lactoglobulin, the main cause of milk allergies in children. The components of CWP have many beneficial effects, including stimulation of both innate and adaptive immunity and anti-inflammatory, anticancer, antibacterial, and antiviral activities. Recently, it has been shown that CWP and its unique components can facilitate the treatment of impaired diabetic wound healing. However, the molecular mechanisms underlying the protective effects of CWP in human and other animal disorders are not fully understood. Therefore, the current review presents a concise summary of the scientific evidence of the beneficial effects of CWP to support its therapeutic use in disease treatment and nutritional intervention.

Comparison of diagnostic tests for suspected cow's milk allergy in children with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. A third of pediatric AD patients have also food allergy. Although food challenge test is gold standard test for the diagnosis of food allergies, they should be administered by experienced physicians, considering that the test is time-consuming and carries some risks. Documentation of the efficacies of specific IgE (sIgE), skin prick test (SPT), and atopy patch test (APT) are important for determining the necessity of oral food challenge tests(OFC). Fifty-three AD patients with suspected cow's milk allergy (CMA) were included in our study. Diet-related questions were asked to the patients. Blood samples were taken for measurement of total blood count, total IgE, and milk sIgE. OFC, SPT, and APT were performed using pasteurized cow milk. The mean age of the study population was 1.4±0.8 years, and the male:female ratio was 1.12. Cow milk allergy was detected in 45.3% of the patients after OFC. A comparison between CMA(+) and CMA(-) patients revealed no significant difference in sIgE positivity (P=0.940), but there was a significant difference in SPT (P=0.000) and APT (P=0.001) positivity. When our study group was divided into immediate reaction, delayed onset reaction, and not reactive subgroups after OFC, efficacy of SPT was more prominent in immediate reaction subgroup while APT was more efficient in delayed reaction subgroup. Our study showed that using SPT test with APT test in allergic reactions with IgE and other mechanisms such as AD will increase the diagnostic yield, thereby reducing the need for OFC.

Principles of personalized diet therapy of cow’s milk allergy in children

Cow’s milk allergy protein (CMPA) is the leading cause of food allergy in infants and young children. The personalized diet prescription, providing individual medical nutrition can be reliable guaranty of effective treatment for diverse range of CMPA symptoms. In spite of the fact that there are a lot of special infant formula in Russia, pediatricians and allergologists have difficulties in choosing appropriate diet. The suggested algorithm of individual option of extensively hydrolyzed proteinbased formula for CMPA patients will help doctors to optimize diet.

Cow's milk allergy in children and adults.

Cow's milk allergy is among the more frequent food allergies in infants and children. Because its suspicion stems from a plethora of symptoms, it is frequently reported. However, the development of a rigorous diagnostic pathway will reduce the diagnosed children to less than 50% of those reported. Cow's milk allergy is the only specific food allergy for which an EBM guideline exists. According to the guidelines (Diagnosis and Rationale for Action against Cow's Milk Allergy), a diagnostic process based on the pre-test probability of this condition is available. Treatments include avoidance, the substitution of cow's milk with an appropriate formula, and in some cases, oral immunotherapy. Treatment choice is also guided by these guidelines.

Cow’s Milk Allergy in Children, from Avoidance to Tolerance

Food allergy is the primary cause of anaphylaxis in paediatric age affecting roughly 4% of children and their families worldwide, and requiring changes in dietary habits. The prognosis for food allergy in children has traditionally been regarded as good for the most frequent allergens, however the prognosis for cow's milk allergy in the pediatric age is currently considered to be worse than previously believed. There is now enough evidence that measures of avoidance for children at risk did not have any preventive effect whatsoever, but they still came to be counterproductive by avoiding the physiological interaction between food allergens and gastrointestinal mucosal immune system. Programs of specific oral tolerance induction (SOTI) have obtained interesting results in the treatment of food allergy supporting the idea that antigen exposure through gastrointestinal section is important to allow the development of tolerance. Nevertheless this approach is not yet considered "ready" for community recommendations. In this paper we describe our experience in the field of SOTI in children with cow's milk allergy.

The Natural History of Food Sensitization in Children With Atopic Dermatitis and the Prognostic Role of Specific Serum IgE

Background: The natural history and the prognostic factors for food tolerance in childhood atopic dermatitis(AD) are poorly understood. Objective: We aimed at investigating the natural course of egg and milk allergy in children affected by AD and food allergy and identifying if the persistence of allergy is associated with high specific serum IgE(sIgE). Methods: The retrospective study included 58 patients affected by AD, aged 9-16 months, with a first clinical examination between 1993 and 2002. Results: Patients with AD and allergy to hen’s egg(N=58) or cow’s milk(N=44) were studied. In most patients milk and egg tolerance was reached before school age, but it was achieved later in children with severe AD and high egg sIgE. Conclusions: The food tolerance is normally reached before school age and, at the time of diagnosis, levels of sIgE&gt;5kU/L for hen’s egg are risk factors for a later tolerance achievement.