Related Articles
Introduction
Cow’s milk protein allergy is common in infants from industrialised countries, but is rarely considered in developing countries due to its variable clinical presentation.
Case presentation
We report on a Tanzanian male infant, who developed blood-stained stool when feeding fresh cow’s milk at the age of three months. After an initial diagnosis of amoebiasis, possible cow’s milk protein allergy was suspected. Further diagnostic work-up was not possible due to lack of resources. After elimination of cow’s milk from the diet, the infant recovered soon.
Conclusion
Cow’s milk protein allergy should be considered more frequently in infants from developing countries, especially when they belong to agropastoralist tribes and are fed cow’s milk early.
doi:10.4076/1757-1626-2-6287
PMCID: PMC2740089
PMID: 19829778
Early introduction of whole cow’s milk may lead to iron deficiency anemia. From a nutritional point of view, it is best to delay the introduction of whole cow’s milk until the infant is one year old. While there is no evidence to suggest adverse clinical sequelae associated with the increased renal solute load in healthy infants, feeding with whole cow’s milk would narrow the margin of safety in situations that may lead to dehydration. Early exposure to cow’s milk proteins increases the risk of developing allergy to milk proteins. Because of the possible association between early exposure to cow’s milk proteins and risk for type 1 diabetes mellitus, breast-feeding and avoidance of commercially available cow’s milk and products containing intact cow’s milk protein during the first year of life are strongly encouraged in families with a strong history of insulin dependent diabetes mellitus. The authors suggest that the optimal food in infancy is human breast milk. If human milk is not available, it is preferred that iron-fortified formulas rather than whole cow’s milk be used during the first year of life.
PMCID: PMC2791650
PMID: 20019947
whole cow’s milk; infancy
Purpose
Food allergies can affect the growth and nutritional status of children with atopic dermatitis (AD). This study was conducted to determine the association between the number of sensitized food allergens and the growth and nutritional status of infants and young children with AD.
Methods
We studied 165 children with AD, aged 5 to 47 months, and who visited the Atopy Clinic of the Seoul Medical Center. We recorded the birth weight, time at which food weaning began, scoring of atopic dermatitis (SCORAD) index, eosinophil counts in peripheral blood, and total serum IgE and specific IgE to six major allergens (egg white, cow's milk, soybean, peanut, wheat, and fish). The height and weight for age and weight for height were converted to z-scores to evaluate their effects on growth and nutritional status. Specific IgE levels ≥0.7 kUA/L, measured via the CAP assay, were considered positive.
Results
As the number of sensitized food allergens increased, the mean z-scores of weight and height for age decreased (P=0.006 and 0.018, respectively). The number directly correlated with the SCORAD index (r=0.308), time at which food weaning began (r=0.332), eosinophil counts in peripheral blood (r=0.266), and total serum IgE (r=0.394). Inverse correlations were observed with the z-scores of weight for age (r=-0.358), height for age (r=-0.278), and weight for height (r=-0.224).
Conclusions
A higher number of sensitized food allergens was associated with negative effects on the growth and nutritional status of infants and young children with AD. Therefore, a thorough evaluation of both growth and nutritional status, combined with adequate patient management, is crucial in pediatric AD patients presenting with numerous sensitized food allergies.
doi:10.4168/aair.2011.3.1.53
PMCID: PMC3005320
PMID: 21217926
Dermatitis atopic; food hypersensitivity; growth; nutritional status
A joint study group on cow's milk allergy was convened by the Emilia-Romagna Working Group for Paediatric Allergy and by the Emilia-Romagna Working Group for Paediatric Gastroenterology to focus best practice for diagnosis, management and follow-up of cow's milk allergy in children and to offer a common approach for allergologists, gastroenterologists, general paediatricians and primary care physicians.
The report prepared by the study group was discussed by members of Working Groups who met three times in Italy. This guide is the result of a consensus reached in the following areas. Cow's milk allergy should be suspected in children who have immediate symptoms such as acute urticaria/angioedema, wheezing, rhinitis, dry cough, vomiting, laryngeal edema, acute asthma with severe respiratory distress, anaphylaxis. Late reactions due to cow's milk allergy are atopic dermatitis, chronic diarrhoea, blood in the stools, iron deficiency anaemia, gastroesophageal reflux disease, constipation, chronic vomiting, colic, poor growth (food refusal), enterocolitis syndrome, protein-losing enteropathy with hypoalbuminemia, eosinophilic oesophagogastroenteropathy. An overview of acceptable means for diagnosis is included. According to symptoms and infant diet, three different algorithms for diagnosis and follow-up have been suggested.
doi:10.1186/1824-7288-36-5
PMCID: PMC2823764
PMID: 20205781
BACKGROUND AND OBJECTIVES:
Infantile colic is a common problem among young infants. Cow’s milk allergy has been suggested as one of the causes. We aimed to investigate the value of the cow’s milk skin test for the diagnosis of cow’s milk allergy in exclusively breast-fed infants with infantile colic.
METHODS:
Exclusively breast-fed infants with infantile colic were enrolled in this study. On the first visit, the average hours of crying of the infant in a 24-h period were recorded and the cow’s milk skin test was performed. If the infant had a positive skin test, elimination of cow’s milk from the mothers’ diet was advised. Infants with negative skin tests were divided into case and control groups. Cow’s milk was eliminated from the diet of mothers in the case group. After 2 weeks, the number of hours of crying were recorded again. The reduction in the crying hours was compared between the two groups using the chi-square test.
RESULTS:
Skin tests were positive in 3 of 114 cases (2.6%) of infantile colic. All three cases recovered completely following elimination of cow’s milk from the mother’s diet. Among the 111 patients with negative skin tests, 77 patients completed the study: 35 in the case group and 42 in the control group. The reduction in crying hours in infants in the case group was not significantly different from that in the control group.
CONCLUSION:
Elimination of cow’s milk from the mothers’ diet is not beneficial for infants with a negative skin test. Infants with a positive skin test may benefit from this management.
doi:10.4103/0256-4947.72269
PMCID: PMC2994164
PMID: 21060160
ABSTRACT
OBJECTIVE
To provide a practical, evidence-based approach to the diagnosis and management of milk protein allergy in infants.
SOURCES OF INFORMATION
MEDLINE was searched from 1950 to March 2008 using the MeSH heading milk-hypersensitivity. Additional sources were derived from reviews found with the initial search strategy. Evidence was levels I, II, and III.
MAIN MESSAGE
Milk protein allergy is a recognized problem in the first year of life; cow’s milk protein allergy is the most common such allergy. Diagnosis is suspected on history alone, with laboratory evaluations playing a supporting role. Confirmation requires elimination and reintroduction of the suspected allergen. Management includes diet modification for nursing mothers and hydrolyzed formulas for formula-fed infants. Assessing the underlying immunopathology can aid in determining prognosis.
CONCLUSION
The therapeutic model presented allows rapid assessment of the presence of allergy, timely management, and surveillance for recurrence of symptoms. Breastfeeding can be continued with attentive diet modification by motivated mothers.
PMCID: PMC2553152
PMID: 18791102
Background
Cow’s milk and hen’s egg are the most frequently encountered food allergens in the pediatric population. Skin prick testing (SPT) with commercial extracts followed by an oral food challenge (OFC) are routinely performed in the diagnostic investigation of these children. Recent evidence suggests that milk-allergic and/or egg-allergic individuals can often tolerate extensively heated (EH) forms of these foods. This study evaluated the predictive value of a negative SPT with EH milk or egg in determining whether a child would tolerate an OFC to the EH food product.
Methods
Charts from a single allergy clinic were reviewed for any patient with a negative SPT to EH milk or egg, prepared in the form of a muffin. Data collected included age, sex, symptoms of food allergy, co-morbidities and the success of the OFC to the muffin.
Results
Fifty-eight patients had negative SPTs to the EH milk or egg in a muffin and underwent OFC to the appropriate EH food in the outpatient clinic. Fifty-five of these patients tolerated the OFC. The negative predictive value for the SPT with the EH food product was 94.8%.
Conclusions
SPT with EH milk or egg products was predictive of a successful OFC to the same food. Larger prospective studies are required to substantiate these findings.
doi:10.1186/1710-1492-8-5
PMCID: PMC3394206
PMID: 22591833
SYNOPSIS
Cow’s milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of immunoglobulin E (IgE-) and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle impact. Definitive diagnosis is based on a supervised oral food challenge (OFC), but convincing clinical history, skin prick testing, and measurement of cow’s milk (CM)-specific IgE can aid in the diagnosis of IgE-mediated CMA and occasionally eliminate the need for OFCs. It is logical that a review of CMA would be linked to a review of soy allergy, as soy formula is often an alternative source of nutrition for infants who do not tolerate cow’s milk. The close resemblance between the proteins from soy and other related plants like peanut, and the resulting cross-reactivity and lack of predictive values for clinical reactivity, often make the diagnosis of soy allergy far more challenging. This review examines the epidemiology, pathogenesis, clinical features, natural history and diagnosis of cow’s milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed.
doi:10.1016/j.pcl.2011.02.005
PMCID: PMC3070118
PMID: 21453810
cow’s milk; soy; bovine; allergy; cross-reactivity; diagnosis; management; natural history; pediatric; children
The 1-hour xylose absorption test was evaluated as method for the diagnosis of cows' milk protein-sensitive enteropathy in a prospective study of 48 infants with diarrhoea clinically suspected to be due to intolerance of cows' milk. The infants were maintained on a lactose and cows milk protein-free diet for 6-8 weeks and then were challenged with cows' milk protein. Jejunal biopsies and the 1-hour xylose absorption test were performed immediately before and 20-24 hours after cows' milk provocation. After milk provocation, 30 infants had clinical, enzymological, and histological relapse, and in 28 of them there was a significant depression of post-provocation blood xylose levels. Six infants had histological and enzymological relapse but clinically they tolerated cows' milk. The post-provocation blood xylose level was depressed in all infants. Ten infants had enzymological relapse without histological or clinical relapse. The post-challenge blood xylose was depressed significantly (greater than 20%) in 3, mildly depressed in 3 (16-18%), and not depressed in four. Two infants clinically, histologically, and enzymologically tolerated cows' milk; in each the post-challenge xylose was depressed (22%, 12%). It appears that the 1-hour blood xylose test is not as reliable as the jejunal biopsy in the diagnosis of cows' milk protein-sensitive enteropathy.
PMCID: PMC2863276
PMID: 7065692
Aim
To study the age when symptoms of adverse reactions to milk occur, in premature and term children, the debut of various symptoms, immunoglobulin E (IgE)- and non-IgE-mediated reactions and the frequency of tolerance at 1 year.
Methods
Six hundred and eight children, 193 premature and 416 term infants, were followed. Symptomatic children were invited to a clinical examination. The criteria for the diagnosis were: histories of suspected cow's milk allergy (CMA) and proven IgE-mediated reactions to cow's milk or positive elimination/challenge tests.
Results
Twenty-seven out of 555 (4.9%) were diagnosed with adverse reactions to cow's milk. All had symptoms before 6 months of age. The main symptoms were: pain behaviour (13), gastrointestinal symptoms (7), respiratory symptoms, (6) and atopic dermatitis (1). One child had proven IgE to cow's milk. Premature and term infants displayed the same symptoms and age of debut. Thirteen children were tolerant to cow's milk at 1 year.
ConclusionAdverse reactions to milk start early in life, with pain behaviour, gastrointestinal, and respiratory symptoms being the most common, and rarely atopic dermatitis. Non-IgE-mediated reactions were the most frequent. Symptoms and age of debut were the same in premature and term infants. Half of the children tolerated cow's milk at age 1.
doi:10.1111/j.1651-2227.2007.00599.x
PMCID: PMC2253707
PMID: 18254909
Adverse reactions to milk; Infancy; Premature children
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 to114 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.
doi:10.3346/jkms.2011.26.9.1152
PMCID: PMC3172651
PMID: 21935269
Milk; Food Hypersensitivity; Immunoglobulin E; Prognosis
Reche M, Pascual C, Fiandor A, Polanco I, Rivero-Urgell M, Chifre R, Johnston S, Martín-Esteban M. The effect of a partially hydrolysed formula based on rice protein in the treatment of infants with cow’s milk protein allergy. Pediatr Allergy Immunol 2010: 21: 577–585. © 2010 John Wiley & Sons A/S
Infants diagnosed with allergy to cow’s milk protein (CMP) are fed extensively hydrolysed cow’s milk formulas, modified soy formulas or even amino acid-based formulas. Hydrolysed rice protein infant formulas have become available and have been shown to be well tolerated by these infants. A prospective open, randomized clinical study to compare the clinical tolerance of a new hydrolysed rice protein formula (HRPF) with an extensively hydrolysed CMP formula (EHF) in the feeding of infants with IgE-mediated cow’s milk allergy. Ninety-two infants (46 boys and 46 girls, mean age 4.3 months, range 1.1–10.1 months) diagnosed with IgE-mediated cow’s milk allergy were enrolled in the study. Clinical tolerance to the formula products was tested. Clinical evaluation included skin prick tests with whole cow’s milk, soya and rice as well as antigens of CMP (beta-lactoglobulin, alpha-lactalbumin, casein and bovine seroalbumin), HRPF and EHF and specific IgE determinations to CMP using CAP technology. Patients were randomized to receive either an EHF based on CMP or a new HRPF. Follow-up was at 3, 6, 12, 18 and 24 months. Growth parameters were measured at each visit. One infant showed immediate allergic reaction to EHF, but no reaction was shown by any infant in the HRPF group. The number of infants who did not become tolerant to CMP during the study was not statistically different between the two groups. Measurement of IgE levels of infants allergic to CMP during the study showed no significant differences between the two formula groups. Growth parameters were in the normal range and similar between groups. In this study, the HRPF was well tolerated by infants with moderate to severe symptoms of IgE-mediated CMP allergy. Children receiving this formula showed similar growth and development of clinical tolerance to those receiving an EHF. In accordance with current guidelines, this HRPF was tolerated by more than 90% of children with CMP allergy and therefore could provide an adequate and safe alternative to CMP-hydrolysed formulas for these infants.
doi:10.1111/j.1399-3038.2010.00991.x
PMCID: PMC2904490
PMID: 20337976
cow’s milk protein allergy; hydrolysed rice protein formula; extensively hydrolysed cow’s milk protein formula
Introduction
Cow’s milk allergy (CMA) is thought to affect 2–3% of infants. The signs and symptoms are nonspecific and may be difficult to objectify, and as the diagnosis requires cow’s milk elimination followed by challenge, often, children are considered cow’s milk allergic without proven diagnosis.
Diagnosis
Because of the consequences, a correct diagnosis of CMA is pivotal. Open challenges tend to overestimate the number of children with CMA. The only reliable way to diagnose CMA is by double-blind, placebo-controlled challenge (DBPCFC).
Therapy
At present, the only proven treatment consists of elimination of cow’s milk protein from the child’s diet and the introduction of formulas based on extensively hydrolysed whey protein or casein; amino acid-based formula is rarely indicated. The majority of children will regain tolerance to cow’s milk within the first 5 years of life.
Conclusions
Open challenges can be used to reject CMA, but for adequate diagnosis, DBPCFC is mandatory. In most children, CMA can be adequately treated with extensively hydrolysed whey protein or casein formulas.
doi:10.1007/s00431-009-0955-7
PMCID: PMC2694929
PMID: 19271238
Cow’s milk allergy; Double-blind placebo-controlled food challenge; DBPCFC; Hypoallergenic formula
Sicherer, Scott H. | Wood, Robert A. | Stablein, Donald | Lindblad, Robert | Burks, A. Wesley | Liu, Andrew H. | Jones, Stacie M. | Fleischer, David M. | Leung, Donald YM | Sampson, Hugh A.
Background
Peanut allergy is typically severe, life-long and prevalent.
Objective
To identify factors associated with peanut sensitization.
Methods
We evaluated 503 infants 3–15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow’s milk and/or egg and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level of ≥ 5 kUA/L was considered likely indicative of peanut allergy.
Results
A total of 140 (27.8%) infants had PN-IgE levels ≥5 kUA/L. Multivariate analysis including clinical, laboratory and demographic variables showed frequent peanut consumption during pregnancy (OR 2.9, 95% CI 1.7–4.9, p < 0.001), IgE levels to milk (p = 0.001) and egg (p < 0.001), male sex (p = 0.02) and non-white race (p = 0.02) to be the primary factors associated with peanut IgE ≥5 kUA/L. Frequency of peanut consumption during pregnancy and breast feeding showed a dose-response association with peanut IgE ≥ 5 kUA/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breastfed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥ 5 kUA/L (OR-4.99, 95% CI-1.69–14.74, p < 0.004).
Conclusions
In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization.
doi:10.1016/j.jaci.2010.08.036
PMCID: PMC3018157
PMID: 21035177
food allergy; sensitization; atopy; peanut allergy
Our aim was to develop guidance for general paediatricians and primary care physicians in diagnosing and managing cow's milk protein allergy in infants. The guidelines were developed by discussion based on existing national recommendations and standards, clinical experience and, whenever possible, evidence from the literature. Separate algorithms cover breast‐fed and formula‐fed infants. The recommendations emphasise the importance of comprehensive history taking and careful physical examination. Patients with severe symptoms need to be referred to a specialist. Elimination of cow's milk protein from the infant's or mother's diet and challenges are the gold standard for diagnosis. This guidance is intended as a basis for local discussion, implementation and prospective evaluation. The algorithms should be regularly assessed using clinical audit standards. Once validated, the diagnostic framework could provide a standardised approach in epidemiological and therapeutic studies.
doi:10.1136/adc.2006.110999
PMCID: PMC2083222
PMID: 17895338
Objective
Cow's milk allergy has different presentations in children and can cause functional bowel symptoms such as chronic constipation. The aims of this study were to investigate the role of cow's milk allergy as a cause of chronic constipation and effect of cow's milk free diet (CMFD) on its treatment in children.
Methods
We performed a randomized clinical study comparing CMFD with cow's milk diet (CMD) in two groups each consisting of 70 patients (age range, 1-13 years) with chronic functional constipation (defined as Rome III criteria). All subjects had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives for at least 3 months without success; also all 140 patients performed skin prick test. The case group received CMFD for 4 weeks. After that they received CMD for 2 extra weeks. The control group received CMD for whole 6 weeks. A response was defined as decreased in signs and symptoms that not fulfilled Rome III criteria after 4 weeks of CMFD and came back to Rome III criteria after 2 weeks of CMD challenge.
Findings
After 4 weeks 56 (80%) patients of the case group responded in comparison to 33 (47.1%) patients in the control group (P=0.0001). In the case group after 2 weeks challenge 24 out of 56 (42.8%) responders developed constipation according to Rome III criteria. With other words, the frequency of cow's milk allergy among constipated patients was 80%. Only one patient had positive skin prick test.
Conclusion
In children, chronic constipation can be a manifestation of cow's milk allergy. At present, although several aspects must be further investigated, a therapeutic attempt with elimination diet is advisable in all children with constipation unresponsive to correct laxative treatment.
PMCID: PMC3533146
PMID: 23429756
Cow's Milk; Milk Allergy; Allergy; Chronic Constipation; Children
Background
Cow's milk allergy (CMA) is the most common food allergy. Clinical manifestations are mediated immediate hypersensitivity and delayed. The allergy study include: specific IgE, prick and patch test. Regarding treatment, this is based on the exclusion diet and the replacement of cow's milk hydrolysates extensive.
Virtually all infants who have cow's milk allergy develop this condition in the first year of life, with clinical tolerance developing in about 80 percent by their fifth birthday.
Methods
Describe the case of a child with CMA, which moves without tolerance and also become sensitized to other foods.
Results
Female with 6 years of age. At 9 months presents watery diarrhea, weight loss and intermittent rash. Initial study (2006): Upper endoscopy: Duodenitis chronic nonspecific, total IgE: 72.60 IU/mL, IgE specific to cow's milk 10.40 IU/mL (Class III) and prick test positive. Exclusion diet starts to cow's milk, its derivatives and beef. Patient improvement. At 2 years, begins with rhinitis and diarrhea reappears with low weight. Colonoscopy (2007): Subacute nonspecific colitis histology. At 3 years old facial angioedema, throat and rash are associated with eating chicken, turkey, carrot and orange juice. New tests: specific IgE cow's milk, 24. 7 IU/mL (class IV), class II chicken. Prick test positive. At 4 years enter kindergarten, restarts with diarrhea and occasional angioedema. Cow's milk specific IgE (January 2009): 66, 6 IU/mL (class V). January 2010: 5 years post anaphylactic shock milk pudding. Besides diarrhea 10 times a day, intermittently throughout the year. Year 2011: intermittent diarrhea and specific IgE to cow's milk is kept in class V.
Conclusions
In this case the patient with CMA which evolved atypically because it has not been able to acquire tolerance. Moreover, awareness is added to other foods during their evolution. A recent study indicated a lower rate of development of clinical tolerance. As assessed by passing a milk challenge, 5 percent were tolerant at age 4 and 21 percent at age 8. Patients with persistent milk allergy have higher cow's milk sIgE levels in the first 2 years of life. Approximately 35 percent developed allergy to other foods.
doi:10.1097/01.WOX.0000412184.40629.eb
PMCID: PMC3512946
Background
Cow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and β-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.
Methods
Eighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).
Results
The CMA group had significantly higher levels of milk-, casein- and β-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.
Conclusions
High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.
doi:10.1186/1476-7961-10-1
PMCID: PMC3398319
PMID: 22212305
casein; cow's milk allergy; IgE; IgG4; ImmunoCAP
Savilahti, Emma M. | Rantanen, Ville | Lin, Jing S. | Karinen, Sirkku | Saarinen, Kristiina M. | Goldis, Marina | Mäkelä, Mika J. | Hautaniemi, Sampsa | Savilahti, Erkki | Sampson, Hugh
Background
Dynamics and balance of allergen specific IgE, IgG4 and IgA binding may contribute to the development of tolerance in cow's milk allergy. Profiling of antibody binding to cow's milk protein epitopes may help in predicting natural history of allergy.
Objective
To investigate differences in IgE, IgG4 and IgA binding to cow's milk epitopes over time between patients with early recovery or with persisting cow's milk allergy.
Methods
We studied serum samples at the time of diagnosis (mean age 7 months), one year later and at follow-up (mean age 8.6 years) from 11 patients with persisting IgE-mediated cow's milk allergy at age 8-9 years, and 12 patients who recovered by age 3 years. We measured the binding of IgE, IgG4 and IgA antibodies to sequential epitopes derived from five major cow's milk proteins with a peptide microarray-based immunoassay. We analyzed the data with a novel image processing method together with machine learning prediction.
Results
IgE epitope binding patterns were stable over time in patients with persisting cow's milk allergy, whereas binding decreased in patients who recovered early. Binding patterns of IgE and IgG4 overlapped. Among patients who recovered early, the signal of IgG4 binding increased while that of IgE decreased over time. IgE and IgG4 binding to a panel of αs1-, αs2-, β-and κ-casein regions predicted outcome with significant accuracy.
Conclusions
Attaining tolerance to cow's milk is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4.
doi:10.1016/j.jaci.2010.03.025
PMCID: PMC3289532
PMID: 20462631
cow's milk allergy; tolerance; epitope; IgE; IgG4; IgA
Background
The therapy for cow's milk proteins allergy (CMPA) consists in eliminating cow's milk proteins (CMP) from the child's diet. Ass's milk (AM) has been recently considered as substitute of CMP. This prospective study investigated tolerance and nutritional adequacy of AM in children with CMPA from Southern Italy.
Methods
Thirty children (aged 6 months to 11 years) with suspected CMPA were enrolled. They underwent skin prick tests and bouble-blind, placebo controlled food challenge to CMP. After confirming the diagnosis of CMPA, patients received fresh AM in a open challenge. Specific serum CMP and AM IgE, and biochemical parameters in blood were also assessed. Auxological evaluations were performed in all subjects at entry (T0) and after 4–6 months (T1) of AM intake.
Results
Twenty-five children resulted elegible for the study, and 24 out of 25 subjects (96%) tolerated AM at the food challenge. Auxological data resulted improved by the end of the study in all patients, while blood biochemical parameters did not vary during the follow-up.
Conclusion
Our data confirm the high rate of AM tolerability in children with moderate symptoms of CMPA. Moreover, we found that AM seems to have nutritional adequacy in subjects with a varied diet.
doi:10.1186/1824-7288-35-19
PMCID: PMC2717565
PMID: 19589131
Background
Cow’s milk allergy is the most common food allergy in young children. In areas outside the United States, milk from other mammals has been studied as a possible and desirable alternative for children with cow’s milk allergy.
Objectives
We chose to further investigate water buffalo’s milk as an alternative for cow’s milk allergic children in the United States.
Methods
Children with cow’s milk allergy were skin prick tested with water buffalo’s milk. Additionally, subjects were followed clinically for 1 year after the test to determine how many of the subjects had persistent cow’s milk allergy.
Results
In total, 30 children, age 8 months to 8 years, were skin prick tested to water buffalo’s milk with 73% (22/30) having a positive test. All children with a negative water buffalo’s milk skin test also had a negative cow’s milk skin test. In follow-up, most (7 of 8) of the children with a negative skin prick test (SPT) to water buffalo’s milk were found to have outgrown their cow’s milk allergy. In comparison, all of the subjects with a positive skin test to water buffalo’s milk had persistent cow’s milk allergy. After adjusting for this, we determined that 96% (22/23) of the children with persistent cow’s milk allergy were positive on skin testing to water buffalo’s milk.
Conclusions
In this population, the vast majority of children with persistent cow’s milk allergy were positive on skin prick testing to water buffalo’s milk. These results indicate that water buffalo’s milk is unlikely to be a successful alternative for children with cow’s milk allergy.
doi:10.1089/pai.2009.0016
PMCID: PMC3218082
PMID: 22102769
Background
Cow's milk allergy (CMA) is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life.
It has been observed that specific IgE (sIgE) towards cow's milk proteins decrease when the age increases.
Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC), that remains the gold standard in the diagnosis of food allergy, by allergometric tests.
Methods
We considered 44 children with CMA diagnosed through OFC who returned to our Allergy and Immunology Pediatric Department between January to December 2010 to evaluate the persistence of allergy or the achievement of tolerance.
On the basis of the history, we performed both allergometric skin tests and OFC in children that were still following a milk-free diet, whereas only allergometric skin tests those that had already undergone spontaneous introduction of milk protein at home without presenting symptoms.
Objective
The aim of this study was to investigate the relationship between the persistence of CMA or the acquisition of tolerance and the results of the end point prick test (EPT).
Results and Discussion
The OFC with cow's milk was performed on 30 children, 4 children were excluded because of a history of severe reactions to cow's milk, and 10 because they had spontaneously already taken milk food derivates at home without problems. 16/30 (53%) children showed clinical reactions and the challenge was stopped, 14/30 (47%) did not have any reaction.
Comparing the mean wheal diameter of every EPT's dilution between the group of allergic children and the tolerant ones, we obtained a significant difference (p < 0.05) for the first 4 dilutions.
We have also calculated sensitivity (SE), specificity (SP), the positive predictive value (PPV) and the negative predictive value (NPV) for each EPT dilution.
Conclusions
EPT is a safe and cheap test, easy to be executed and that could provide good prediction of the outcome of OFC; so it might be used to avoid OFC-induced anaphylaxis in children affected by CMA. It can also help avoiding dietetic restrictions in tolerant children who show sensitization towards cow's milk proteins.
doi:10.1186/1824-7288-37-52
PMCID: PMC3220633
PMID: 22053846
Cow's milk proteins allergy; end point prick test; food oral challenge; tolerance
Eleven infants who were suspected clinically of having cows' milk protein sensitive enteropathy were fed with a protein hydrolysate formula for six to eight weeks, after which they had jejunal and rectal biopsies taken before and 24 hours after challenge with cows' milk protein. When challenged six infants (group 1) developed clinical symptoms and five did not (group 2). In group 1 the lesions developed in both the jejunal mucosa (four infants at 24 hours and one at three days), and the rectal mucosa, and the injury was associated with depletion of alkaline phosphatase activity. Infants in group 2 were normal. It seems that rectal injury that develops as a direct consequence of oral challenge with the protein in reactive infants may be used as one of the measurements to confirm the diagnosis of cows' milk protein sensitive enteropathy. Moreover, ingestion of such food proteins may injure the distal colonic mucosa without affecting the proximal small gut in some infants.
PMCID: PMC1792711
PMID: 2817945
Background
Children with cow’s milk allergy (CMA) need a cow’s milk protein (CMP) free diet to prevent allergic reactions. For this, reliable allergy-information on the label of food products is essential to avoid products containing the allergen. On the other hand, both overzealous labeling and misdiagnosis that result in unnecessary elimination diets, can lead to potentially hazardous health situations. Our objective was to evaluate if excluding CMA by double-blind placebo-controlled food challenge (DBPCFC) prevents unnecessary elimination diets in the long term. Secondly, to determine the minimum eliciting dose (MED) for an acute allergic reaction to CMP in DBPCFC positive children.
Methods
All children with suspected CMA under our care (Oct’05 - Jun’09) were prospectively enrolled in a DBPCFC. Placebo and verum feedings were administered on two randomly assigned separate days. The MED was determined by noting the ‘lowest observed adverse effect level’ (LOAEL) in DBPCFC-positive children. Based on the outcomes of the DBPCFC a dietary advice was given. Parents were contacted by phone several months later about the diet of their child.
Results
116 children were available for analysis. In 76 children CMA was rejected. In 60 of them CMP was successfully reintroduced, in 2 the parents refused introduction, in another 3 the parents stopped reintroduction. In 9 children CMA symptoms reappeared. In 40 children CMA was confirmed. Infants aged ≤ 12 months in our study group have a higher cumulative distribution of MED than older children.
Conclusions
Excluding CMA by DBPCFC successfully stopped unnecessary elimination diets in the long term in most children. The MEDs form potential useful information for offering dietary advice to patients and their caretakers.
doi:10.1186/1475-2891-12-22
PMCID: PMC3599188
PMID: 23394146
Cow’s milk allergy; Cow’s milk protein; Double-blind placebo-controlled provocation; Milk hypersensitivity; Minimum eliciting dose
Background
Intestinal malrotation is an incomplete rotation of the intestine. Failure to rotate leads to abnormalities in intestinal positioning and attachment that leave obstructing bands across the duodenum and a narrow pedicle for the midgut loop, thus making it susceptible to volvulus. One of the important differential diagnoses for malrotation is an allergy to cow’s milk. Several studies have described infants with surgical gastrointestinal diseases and cow’s milk allergy. However, to our knowledge, no study has reported infants with intestinal malrotation who have been symptomatic before surgery was performed and have been examined by allergen-specific lymphocyte stimulation test and food challenge tests with long-term follow-up.
Case presentation
The patient was a Japanese male born at 39 weeks of gestation. He was breast-fed and received commercial cow’s milk supplementation starting the day of birth and was admitted to our hospital at 6 days of age due to bilious vomiting. Plain abdominal radiography showed a paucity of gas in the distal bowel. Because we demonstrated malpositioning of the intestine by barium enema, we repositioned the bowel in a normal position by laparotomy. The patient was re-started on only breast milk 2 days post surgery because we suspected the presence of a cow’s milk allergy, and the results of an allergen-specific lymphocyte stimulation test showed a marked increase in lymphocyte response to kappa-casein. At 5 months of age, the patient was subjected to a cow’s milk challenge test. After the patient began feeding on cow’s milk, he had no symptoms and his laboratory investigations showed no abnormality. In addition, because the patient showed good weight gain and no symptoms with increased cow’s milk intake after discharge, we concluded that the present case was not the result of a cow’s milk allergy. At 1 year, the patient showed favorable growth and development, and serum allergy investigations revealed no reaction to cow’s milk.
Conclusion
When physicians encounter infants with surgical gastrointestinal disease, including intestinal malrotation, they should consider cow’s milk allergy as a differential diagnosis or complication and should utilize food challenge tests for a definitive diagnosis.
doi:10.1186/1756-0500-5-481
PMCID: PMC3490812
PMID: 22943656
Allergen-specific lymphocyte stimulation test; Cow’s milk allergy; Food challenge test; Infant; Intestinal malrotation