Cow's Milk Allergy In Children Research Articles

Research progress on the mechanism of probiotics regulating cow milk allergy in early childhood and its application in hypoallergenic infant formula.

Some infants and young children suffer from cow's milk allergy (CMA), and have always mainly used hypoallergenic infant formula as a substitute for breast milk, but some of these formulas can still cause allergic reactions. In recent years, it has been found that probiotic nutritional interventions can regulate CMA in children. Scientific and reasonable application of probiotics to hypoallergenic infant formula is the key research direction in the future. This paper discusses the mechanism and clinical symptoms of CMA in children. This review critically ex- amines the issue of how probiotics use intestinal flora as the main vector to combine with the immune system to exert physiological functions to intervene CMA in children, with a particular focus on four mechanisms: promoting the early establishment of intestinal microecological balance, regulating the body's immunity and alleviating allergic response, enhancing the intestinal mucosal barrier function, and destroying allergen epitopes. Additionally, it overviews the development process of hypoallergenic infant formula and the research progress of probiotics in hypoallergenic infant formula. The article also offers suggestions and outlines potential future research directions and ideas in this field.

The Need for Culturally Appropriate Food Allergy Management Strategies: The Indian Milk Ladder.

Cow's milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and, with a few exceptions, presents in the first few months of life. Baked-milk-containing diets are well tolerated in the majority of milk-allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to an infant's diet in small amounts may enhance the outgrowth of their milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. We convened an expert group to develop a comprehensive milk ladder based on the calculated milk protein content of Indian foods. To validate the milk ladder, the foods chosen for the ladder were analyzed and the ladder was re-evaluated based on the cooked milk protein content. Combining expert consensus and validation of milk protein content, we created the world's first milk ladder containing Indian foods. This is the first ladder that provides information on the timing and temperature of cooking, with validated milk protein content. This is the first milk ladder based on the unique features of Indian food habits built by the consensus of Indian experts along with international collaboration with laboratory quantification of milk protein in each step. We believe the "The Indian Milk Ladder" will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India, but in countries world-wide where these foods are commonly consumed.

Bifidobacteria modulate immune response in pediatric patients with cow's milk protein allergy.

In children with an allergy to cow's milk proteins (CMA), the altered composition of intestinal microbiota influences the immune tolerance to milk proteins (CMP). This study aims to investigate the effect of probiotics on the phenotype and activation status of peripheral basophils and lymphocytes in a pediatric CMA cohort. CMA children underwent 45 days of treatment with Bifidobacteria. The basophil degranulation and the immune phenotype of B cells, T helper cells, and regulatory T cells were analyzed in peripheral blood at diagnosis (T0), after a 45-day probiotic treatment (T1), and 45 days after the probiotic wash-out (T2). We observed in probiotic-treated CMA patients a decrease in naive T lymphocytes. Among the CD3+ cell subsets, both naive and activated CD4+ cells resulted markedly reduced after taking probiotics, with the lowest percentages at T2. A decreased basophil degranulation was observed in response to all analyzed CMP at T1 compared to T0. The probiotic treatment resulted in a decrease of circulating naive and activated CD4+ T cells, as well as degranulating basophils. These data suggest that the Bifidobacteria could have a beneficial effect in the modulation of oral tolerance to CMP. ISRCTN69069358. URL of registration: https://www.isrctn.com/ISRCTN69069358 . Probiotic treatment with Bifidobacteria induces a reduction of both naive and activated circulating CD4+ T cells in pediatric patients with cow's milk allergy (CMA). The probiotic supplementation induces a decreased basophil degranulation. The immunological tolerance persists even after 45 days of the probiotic wash-out. Bifidobacteria in vivo supplementation down-modulates the activation of innate and adaptive immunity in pediatric patients with cow's milk allergy. Bifidobacteria contribute to the development of immune tolerance in CMA patients.

Hypoallergenicity assessment of an extensively hydrolyzed whey-protein formula in cow's milk allergic infants.

Background Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA).ObjectivesHypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey‐protein formula (eHWF) in CMA children were assessed.MethodsIn this prospective, randomized, international, multi‐center study (Trial NL3889), 34 children with confirmed CMA (74% IgE‐mediated) underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) with an eHWF developed with non‐porcine enzymes, supplemented with prebiotic short‐chain galacto‐ and long‐chain fructo‐oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7‐day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16‐weeks follow‐up.ResultsOf the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE‐mediated CMA) completed the DBPCFC and 7‐day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow‐up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient.ConclusionsThe newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability.Trial registrationTrial NL3889, https://www.trialregister.nl/trial/3889.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - IV - A quality appraisal with the AGREE II instrument.

BackgroundSince the publication of The World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines in 2010, a number of other guidelines, expert opinions, and position papers relating to the management of cow's milk allergy (CMA) have been published. We aimed to systematically review the quality of the guidelines on CMA diagnosis and management in children and/or adults published between 2010 and 2020.MethodsThe MEDLINE, EMBASE, ISI Web of Science, World Health Organization Global Index Medicus, and Turning Research into Practice databases as well as website guideline repositories were searched from January 2010 until May 2020. Any clinical practice recommendations and/or guidelines focusing on the diagnosis and management of CMA in children and/or adults developed or endorsed by professional scientific societies or organizations were included. The guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool, a 23-item tool organized within 6 domains and 2 global rating items.ResultsWe included 12 guidelines; 8 were developed by national and 4 by international organizations. The quality scores for each domain varied: of all domains, the clarity of presentation domain had the highest median score (92%; Q1-Q3 81–100%), whereas rigor of development had the lowest median score (30%; Q1-Q3 15–67%). The median scores (Q1-Q3) for individual domains were as follows: scope and purpose 82% (70–99%), stakeholder involvement 63% (21–79%), rigor of development 30% (15–67%), clarity of presentation 92% (81–100%), applicability 68% (57–75%), and editorial independence 75% (69–100%). The median overall score was 70% (58–89%). Only 1 guideline (from the National Institute for Health and Care Excellence [NICE]) achieved top ratings (100%) in five domains and the overall score. Three guidelines (from the NICE, the British Society for Allergy & Clinical Immunology [BSACI] and WAO) achieved the highest ratings (100%) in at least 3 domains and the overall score.ConclusionThe majority of identified guidelines were of good or very good quality. However, the weakest point was the rigor of development domain, mostly due to unclear description of strengths and limitations of the body of evidence and the procedure for updating the guidelines.

Immunonutrition for Pediatric Patients With Cow's Milk Allergy: How Early Interventions Could Impact Long-Term Outcomes.

Cow's milk allergy (CMA) is one of the most common food allergies and one of the main causes of food-induced anaphylaxis in the pediatric age. Moreover, up to 45% of CMA children develop other atopic manifestations later in life, a phenomenon commonly named atopic march. Thus, CMA imposes a significant cost to health care systems as well as to families, and has emerged as one of the most expensive allergic diseases. The immunonutrition strategy builds its foundation on the ability of selected dietary factors to modulate immune system development and function. Recent studies highlighted the potential of immunonutrition in the management of CMA. This review is focused on the mechanisms and long-term clinical outcomes of the immunonutrition approach in children with CMA.

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.

Cow's Milk Allergy: the Relevance of IgE.

Cow's milk allergy (CMA) accounts for most diagnosed food allergies, mainly in the first year of life.1 CMA can cause severe anaphylaxis.2 CMA management is based on strict avoidance and the prescription of rescue medication. Cow's milk (CM) contains more than 40 proteins, including casein (Bos d 8), -lactalbumin (Bos d 4), and -lactoglobulin (Bos d 5), identified as major milk allergens.1 Serum specific IgE (sIgE) to casein characterized patients with persistent CMA,3 CM tolerance,4 and reactivity to baked milk.5 Oral immunotherapy (OIT) for CMA has been used with interesting outcomes as it may induce immunologic tolerance.1,2 However, a safety perspective represents a relevant concern, because reactions to OIT are frequent1,2 It has been demonstrated that sIgE to raw CM >50 kUA/L predicted not-tolerated OIT.6 Molecular-based allergy diagnostics have now become recently available in clinical practice. This method allows for defining and characterizing the sensitization profile that identifies potentially dangerous proteins and suggests a more precise prognosis. In this regard, Cingolani and colleagues reported that component resolved diagnosis had a good ability to define 2 phenotypes of CMA children: high-anaphylaxis and milder-risk.7 In particular, these phenotypes can be differentiated through measuring the level of sIgE to Bos d 8. We now report our experience concerning a retrospective cohort. This observational and retrospective experience evaluated the usefulness of ImmunoCAP and ISAC (please describe company, city, country) to detect anaphylaxis after CM ingestion. We evaluated children with CMA diagnosis who consecutively visited the Istituto Gaslini (a third tier children's hospital) in the last year. CMA diagnosis was performed on suggestive history consistent with CM sensitization (i.e. symptom occurrence after milk ingestion), documented milk sensitization, and a positive food challenge test. Anaphylaxis was defined according to validated criteria: briefly, suggestive history (sudden occurrence of symptoms, involving at least two systems, such as gastrointestinal and/or cutaneous and/or respiratory and/or cardiovascular after milk ingestion) consistent with documented CM sensitization.1 Serum sIgE to: raw CM allergen, Bos d 4, 5, and 8 were measured by the quantitative ImmunoCAP method and the semi-quantitative microarray-ISAC method (Thermo Fisher Italy). We Evaluated 53 patients (20 with anaphylaxis and 33 with CMA). Children with anaphylaxis presented: skin symptoms (89%), respiratory complaints (77%), gastrointestinal features (57%), and cardiovascular symptoms (11%). Children with CMA presented: skin symptoms (71%), gastrointestinal features (65%, mainly vomiting), and respiratory complaints (58%). The Table shows the clinical and immunologic characteristics of the 2 groups. The significant prevalence for male gender in anaphylaxis was consistent with that of Cingolani's study. The age was significantly lower in the anaphylaxis group, it conflicted with the findings of that study (surprisingly the age was particularly old in regards to CMA). Serum sIgE levels to raw CM allergen were significantly higher in the anaphylaxis group; however, there was no significant difference between the two groups for all molecular components as measured by both the ImmunoCAP and ISAC method. Table Clinical and imunological characteristics of patients Receiver operating characteristic (ROC) analysis showed that raw CM ImmunoCAP had a good specificity (86.7%), but weak sensitivity (52.9%), fair positive (69.2%), and negative (76.5%) predictive value, with Diagnostic Odds Ratio (ORDiagn) 7.3. The assessment of molecular components by ImmunoCAP was unsatisfactory in regards to area under the ROC curve (AUC), sensitivity, and specificity, despite the fair positive and negative values. The micro-assay ISAC method was also unreliable in our setting. We believe that the diagnostic work-up for CMA should consider a molecular-based allergy diagnostic as well as a raw allergen assessment to obtain more useful information for the management and possible identification of risk factors.

Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow's milk allergy.

Cow's milk allergy (CMA) is a frequent food allergy in young children. The oral food challenge is the gold standard for diagnosis, and there is currently no reliable biological test. Our aim was to evaluate the diagnostic potential of a functional assay quantifying allergen-specific Th2 cells in CMA children. A total of 29 children aged 2.8-10.5years underwent a double-blind, placebo-controlled food challenge (DBPCFC) to cow's milk. Blood was collected before performing the DBPCFC, and peripheral mononuclear cells were cultured in an 18-h ELISpot assay with casein, α-lactalbumin, or β-lactoglobulin. Numbers of antigen-specific IL-4- and IL-13-secreting lymphocytes and serum-specific IgE, IgG4, and total IgE levels were assessed. Receiver operating characteristic (ROC) curves were generated. A total of 17 (59%) children reacted to cow's milk and were therefore considered as allergic to cow's milk (CMA). The mean number of casein-specific IL-4- and IL-13-secreting T cells was higher in CMA than in non-CMA children (P=0.009, 0.004, respectively). Moreover, it was inversely correlated with the cumulative dose of cow's milk tolerated (P=0.003, 0.0009, respectively). ROC curve of combined IL-4 and IL-13 analysis showed an area under the curve of 0.98 (95% CI 0.90-1.06). For a cutoff of 10 IL-4- and 12 IL-13-secreting T cells, sensitivity and negative predictive value were 100%. Enumeration of casein-specific IL-4- and IL-13-secreting T cells appears a promising tool to improve diagnosis and, if confirmed in larger studies, could permit less frequent use of the oral food challenge.

Perinatal environmental influences on goat's and sheep's milk allergy without cow's milk allergy

Cow's milk (CM) allergy is the most common food allergy in children, and it can coincide with goat's and sheep's milk (GSM) allergy because of high sequence homology between the corresponding proteins. [1] Jarvinen K.M. Chatchatee P. Mammalian milk allergy: clinical suspicion, cross reactivities and diagnosis. Curr Opin Allergy Clin Immunol. 2009; 9: 251-258 Crossref PubMed Scopus (79) Google Scholar Conversely, GSM allergy without CM allergy is extremely rare and mainly reported in countries with higher consumption of GSM products. [2] Rodriguez del Rio P. Sanchez-Garcia S. Escudero C. et al. Allergy to goat's and sheep's milk in a population of cow's milk allergy children treated with oral immunotherapy. Pediatr Allergy Immunol. 2012; 23: 128-132 Crossref PubMed Scopus (32) Google Scholar The reasons for the development of GSM allergy without CM allergy are unclear, but identical twin studies could shed light on this issue. We describe a case of monoamniotic identical twin girls with disparate food allergy. Twin A developed GSM allergy without CM allergy, and twin B has not yet manifested any food allergy.

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

IntroductionPatients 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 methodsThe 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.ResultsThe 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.ConclusionsOur 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.

Oral immunotherapy for cow's milk allergy

Cow's milk allergy (CMA) is common in children and may lead to severe systemic reactions. Avoidance of the ingestion of cow milk is the only effective approach, but this does not exclude the inadvertent or accidental ingestion, or the assumption of milk hidden in other foods. As no pharmacological treatment is available, specific desensitization has been considered an attractive strategy. In the last years, several trials of oral desensitization to cow milk, with different protocols, were published. Overall the results were favourable and demonstrated the achievement of a full tolerance in a high percentage of children. Mild side effects that can be easily managed by slowing the desensitization were reported frequently. The discontinuation of the procedure was necessary in less than 20% of children, on average, due to severe side effects. Oral immunotherapy (oral desensitization) seems to be a promising treatment strategy for cow milk allergy in children that can be applied also to other foods such as eggs or peanuts.

Camel milk: An alternative for cow's milk allergy in children

Treatment of cow's milk allergy (CMA) in children includes avoidance of cow's milk and providing a milk substitute. This study was designed to determine whether CMA children could safely consume camel's milk as an alternative, and skin-prick test (SPT) to camel's milk could be a reliable tool in selecting them. Between April 2007 and February 2010, children with confirmed CMA seen at the Allergy-Immunology Clinic, Hamad Medical Corp., were enrolled into this prospective cohort study. Subjects had a detailed history and medical examination, complete blood count with differential count, total serum IgE, and specific IgE test and SPT to cow's milk. Patients with positive SPT and an elevated cow's milk-specific IgE had negative SPT to camel's milk. Of 35 children (23 male and 12 female children) aged 4-126 months (median, 21 months), 23 patients (65.7%) presented with acute urticaria, 17 (48.6%) with atopic dermatitis, 9 (25.7%) with anaphylaxis, 8 (22.9%) with failure to thrive, and 5 (14.3%) with chronic vomiting. Twenty-eight patients (80%) had family history of allergy. Twenty-six patients (74.3%) were breast-fed for ≤18 months. Mean white blood cell count was 9860.5 cells/μL, absolute eosinophil count was 1219 cells/μL, IgE was 682 IU/mL, and cow's milk-specific IgE was 22.01 kU/L. Only 7 patients (20%) had positive SPT to camel's milk and 28 (80%) were negative to camel's milk. All patients with negative SPT took camel's milk without any reactions. In children with CMA, SPT is a reliable clinical test in ruling out reactivity to camel's milk so these children could safely take camel's milk as an alternative nutrient.

Basophil activation test based on the expression of CD203c in the diagnostics of cow milk allergy in children

BackgroundDetection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis.ObjectiveThe aim of this study was to assess the potential of this technique for the diagnosis of pediatric cow milk allergy.Material and methodsThe quantification of total and specific IgE and basophil activation test were performed to evaluate cow milk allergic (n = 9), and non-allergic children (n = 15).ResultsAllergen-induced basophil activation was detected as a CD203c up-regulation. The expression of CD203c antigen on basophils was measured with flow cytometry. The antigen CD203c was detected on 15.4 ± 10.2% basophils from allergic children after incubation with specific allergens in concentration 1:10, whereas in the control group there were 3.0 ± 1.5% of basophils positive for this molecule (P < 0.05). Stimulation with allergen diluted 1:500 resulted in activation of 15.3 ± 11.2% of basophils in allergic children and 3.8 ± 2.3% of cells in the control group (P < 0.05). Positive results of an allergenicity test (above the cut- off level of 10%) were obtained in 7 out of the 9 allergic children. In 5 cases, the cutoff level was reached with both dilution of allergens (1:10 and 1:500). In 1 patient, positive stimulation was observed after stimulation with allergen diluted 1:10 and in another case only 1:500 resulted in stimulation of more then 10% of basophils. In no child of the control group, stimulation above 10% was noted.ConclusionsThis study demonstrates that the analysis of allergen-induced CD203c up-regulation with flow cytometry is a reliable tool for the diagnosis of cow milk allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity.

Evaluation of the utility of atopy patch testing, skin prick testing, and total and specific IgE assays in the diagnosis of cow's milk allergy

Information on the utility of atopy patch testing (APT) in the diagnosis of food allergy is derived from studies of children with atopic dermatitis. To evaluate the usefulness of APT in the diagnosis of cow's milk allergy (CMA) and to determine interleukin 4 and interferon-gamma production by peripheral blood mononuclear cells. Thirty-seven children (median age, 11 months) with suspected CMA who had a variety of symptoms that involved many organ systems were evaluated using double-blind placebo-controlled food challenges (DBPCFCs), and the performances of milk specific IgE, skin prick testing (SPT), and APT were determined. To search for a possible relationship between the diagnostic tests and the TH1/TH2 immune response, we measured interferon-gamma and interleukin 4 levels in the supernatants of peripheral blood mononuclear cell cultures. Seventeen children with positive DBPCFC results and 6 with a history of anaphylaxis were diagnosed as having CMA. The combined use of APT and SPT had a sensitivity of 100% and a negative predictive value of 100% but a specificity of 50% and a positive predictive value of 76%. The addition of milk specific IgE assays to APT and SPT did not improve these values. Pattern of cytokine secretion was not associated with APT positivity or a specific response to DBPCFC. Atopy patch testing may be a useful adjunct to SPT in excluding CMA in children who have allergic manifestations other than atopic dermatitis. However, DBPCFCs are still necessary in the presence of positive test results.

Clinical Observations of Gastrointestinal Cow Milk Allergy in Children According to a New Classification

Clinical Observations of Gastrointestinal Cow Milk Allergy in Children According to a New Classification

Concurrent cereal allergy in children with cow's milk allergy manifested with atopic dermatitis.

There is increasing consensus about the significance of food allergens in the pathogenesis of atopic dermatitis (AD) in infancy and childhood, with cow's milk and egg accounting for most of the reactions. Previous studies have indicated that multiple food sensitization, such as cereals, is very common in patients with cow's milk allergy (CMA). Evidence is lacking, however, as to its clinical relevance. The purpose of this study was to determine the concurrent occurrence of cereal allergy among children with challenge-proven CMA who have residual symptoms, such as AD and/or gastrointestinal symptoms, during cow's milk elimination diet. Further, we sought to evaluate the utility of patch testing in prescreening foods other than cow's milk behind allergic symptoms in children. The study population comprised 90 children, aged from 2.5 to 36 months (mean 1.1 years), with challenge-proven CMA. As a result of residual symptoms during meticulous cow's milk elimination diet (AD: n=80, and gastrointestinal: n=10), the children were put on a cereal elimination diet (oats, wheat, rye, and barley) and skin prick tests (SPT) and patch testing with cereals were performed. Open cereal challenge was performed to confirm cereal allergy. Cereal challenge was positive in 66 (73%) of the children with CMA. Of them, 17% reacted with immediate reactions and delayed-onset reactions were seen in 83% of the children. SPT was positive in 23%, patch test in 67%, and either SPT or patch test was positive in 73% of the children with cereal allergy. SPT gave the best positive predictive value, whereas SPT together with patch test gave the best negative predictive value. Residual symptoms, such as eczema or gastrointestinal symptoms in CMA children may be a sign of undetected allergy to other food antigens. SPT with cereals aids in diagnosing cereal allergy in small children, especially when used together with patch testing.

A similar high level of immunoglobulin A and immunoglobulin G class milk antibodies and increment of local lymphoid tissue on the duodenal mucosa in subjects with cow's milk allergy and recurrent abdominal pains

In previous studies, we have reported endoscopic and histological alterations locally on the gastrointestinal (GI) tract associated with a gastrointestinal type of cow's milk allergy. In this study, we sought to further characterize endoscopic, and immunological findings in these children. We also hypothesized that the same type of immune responses might also be found in children with unexplained and recurrent abdominal pains. We did a gastroduodenoscopy for persistent GI symptoms, examined the mucosal histology of the small intestine and measured the antibodies to whole cow's milk and its fractions with an enzyme-linked immunosorbent assay (ELISA) in a consecutive series of 22 subjects with untreated and 14 with treated cow's milk allergy (CMA) and 44 with recurrent abdominal pains (RAP). The immunological findings of the study subjects were compared with 54 controls. Lymphonodular hyperplasia (LNH) of the duodenum was the main endoscopic finding in 11 subjects (50%) with untreated and 5 (36%) with treated CMA. It was also found in 6 of 44 subjects with RAP. Compared with the controls, the patients with CMA showed significantly higher levels of IgA class antibodies to whole milk (p = 0.003) and betaLG (p < 0.0001). Of the IgG class antibodies to betaLG (p = 0.032), BSA (p < 0.0001) and alphaCAS (p < 0.0001) were significantly higher. The patients with LNH of the duodenal bulb as the main endoscopic finding showed significantly higher values of IgG class antibodies to betaLG (p = 0.01) and alphaCAS (p = 0.005). Interestingly, the patients examined for RAP showed a similar increment in the pattern of whole milk and specific milk protein antibodies as the CMA children. In conclusion this study showed that gastrointestinal CMA beyond infancy is significantly associated with high levels of IgG and IgA class antibodies to milk and its fractions. As high levels of these antibodies and LNH of the duodenal bulb were also found in subjects with RAP, the study further suggests that gastrointestinal CMA might be one major reason for RAP.

Intestinal permeability in children: variation with age and reliability in the diagnosis of cow's milk allergy

To analyse to what extent age may alter intestinal permeability (IP) in children and to assess its reliability according to clinical manifestations in cow's milk allergy (CMA). A routine prospective study was performed in 200 children (12.5+/-23 mo, 0.5-168 mo) presenting with clinical manifestations suggesting CMA. Controls (n = 105) were those with a negative cow's milk challenge, whereas CMA children (n = 95) fulfilled ESPGHAN criteria. Permeability was measured as a percentage of urinary excretion of lactitol (L, %) and mannitol (M, %) (0.1 g/kg for each, oral absorption after a 6 h fast, 5 h urine collection, analysis by gas chromatography) and determination of the L/M ratio (L/M, %). In control children, L/M correlated negatively with age (r -0.33, p = 0.0006), whereas in those with CMA no correlation was found. Median L/M was significantly higher in CMA children (n = 95) than in controls (n = 105), 4.35+/-7.57% (95% CI 5.30-8.39%) vs 1.97+/-0.87% (95% CI 1.76-2.09%), (p = 0.0001). With a L/M cut-off value defined as mean + 2 SD of controls, in CMA IP exhibited a 68% sensitivity and a 77% negative predictive value. The highest sensitivity (70%) was seen at ages 6-12 mo and the lowest (58%) at age more than 3 y. An abnormal IP was seen in 80% of CMA children with digestive manifestations, in 43% with extra-digestive, 68% with mixed and 40% with anaphylactic manifestations. IP correlates negatively with age in control children and is altered in children with CMA. The test is at its most accurate in the diagnosis of CMA when done at ages 6-12 mo, when there are digestive manifestations.

Type I Allergy to Cow Milk Proteins in Adults

To determine the clinical and serological characteristics of type I food allergy to cow milk proteins in adults, we investigated all 34 patients (aged from 16 to 58 years) who were diagnosed between 1981 and 1991 to have IgE-mediated reactions to cow milk and cheese. Women represented 91.2% of the study group and 39% of them suffered from the first symptoms during or soon after a pregnancy. So far, 47% of the patients were nonatopic and showed a monovalent sensitization to cow milk proteins. According to RAST results (score > or = 2) the predominant allergen was casein with a sensitization frequency of 71%, whereas sensitization to whey proteins (alpha-lactalbumin and beta-lactoglobulin) in this adult group was rare. In cow milk allergy (CMA) patients, significantly lower levels of milk-specific IgG were observed than in normal controls. The main organ manifestations of CMA in adults were the respiratory tract and the skin, with gastrointestinal and cardiovascular symptoms occurring less often than in children. Only 28% of CMA adults could enjoy an unlimited symptom-free intake of milk products after 4 years of disease. Compared with the existing studies on CMA in children, the results suggest that allergies to cow milk proteins in adults are less frequent and tend to persist longer. They are likely to be misdiagnosed for years due to symptoms that initially often refer to only one organ system such as the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)