Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy

To cite this article: Savilahti EM, Viljanen M, Kuitunen M, Savilahti E. Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy. Pediatric Allergy Immunology 2012: 23: 590-596. ABSTRACT: Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to β-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to β-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to β-lactoglobulin than infants with negative DBPC CM challenge (p?=?0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p?=?0.04). The relation of CM IgE to β-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p?相似文献   

Cow's milk protein intolerance and chronic constipation in children

Cow's milk protein (CMP) allergy was investigated in 25 children (age-range 3 months to 11 years) with chronic constipation. A diagnosis of constipation was made on the basis of a history of painful elimination of hard stools for at least 1 month, whether or not associated with a reduced frequency of stools or soiling. The children were evaluated using clinical parameters and the following laboratory tests: total serum immunoglobulin E (IgE); specific IgE (radioallergosorbent test [RAST]) for whole cow's milk, α-lactoalbumin, β-lactoglobulin, and a food group; and skin-prick tests with whole milk, α-lactoalbumin, β-lactoglobulin, and casein. Following the evaluation, the children were submitted to a CMP-free diet for a period of 4 weeks. In seven patients (28%), constipation disappeared during the CMP-free diet and reappeared within 48–72 h following challenge with cow's milk. In two infants a rectal biopsy revealed allergic colitis and they therefore did not undergo the challenge. High serum levels of total IgE were observed in five of the children who showed a clinical improvement (71%), a positive skin-test in two (29%), and detectable specific IgE in two (29%). These results suggest that CMP allergy or intolerance should be considered as a cause of chronic refractory constipation in children, although the underlying mechanism still require further investigation.     

THE SPECTRUM OF COW'S MILK ALLERGY IN CHILDHOOD Clinical, Gastroenterological and Immunological Studies

Abstract. Seventeen of 52 children suspected of having cow's milk allergy had this diagnosis confirmed after milk challenge in hospital. A broad spectrum of reactions was observed including skin eruptions, respiratory symptoms and gastrointestinal disturbance. Not all patients with gastrointestinal symptoms showed small bowel mucosal damage. Only patients with skin reactions had positive skin tests. IgA deficiency and IgE elevation were common. Four patients had symptoms within 3 days of birth. Twelve children tolerated cow's milk by three years of age. Cow's milk allergy can cause a variety of symptoms. Challenge with milk for several days may be required before allergic manifestations can be demonstrated.     

CLINICAL AND IMMUNOLOGICAL ASPECTS OF FOOD ALLERGY IN CHILDHOOD I. Estimation of IgG, IgA and IgE Antibodies to Food Antigens in Children with Food Allergy and Atopic Dermatitis

Abstract Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

L'allergie aux hydrolysats de protéines du lait de vache. À propos de huit cas

BACKGROUND: The use of extensively hydrolyzed protein formulas is the best alternative for children with cow's milk allergy, though cases of allergies to hydrolyzed proteins have been reported. The aim of this study was to clarify from our experience the diagnostic, evolutive and therapeutic aspects of allergies to extensively hydrolyzed protein formulas. PATIENTS AND METHODS: We report eight cases of allergy to extensively hydrolyzed protein formulas seen between 1985 and 1998. The diagnostic criteria for allergy were either the appearance of immediate anaphylactic reactions after the ingestion of protein hydrolysate or a positive challenge test with the protein hydrolysate. RESULTS: Four children developed immediate anaphylactic symptoms after ingesting protein hydrolysate, and four children demonstrated subacute or chronic gastrointestinal symptoms. All children who developed acute anaphylactic symptoms had positive skin tests and specific IgF, antibodies (RAST) to cow's milk and/or hydrolyzed proteins. Conversely, in the four children with chronic gastrointestinal symptoms, skin tests and specific IgE antibodies were negative in three cases, but intestinal histology was abnormal in all of them when they were fed with a protein hydrolysate; this became normal after excluding the hydrolysate (data available in only two cases). Three children tolerated another protein hydrolysate form (whey vs. casein), four children had a favourable outcome when fed with human milk, and an amino-acid-based formula was successfully used in the most recent case. Nonhydrolyzed cow's milk proteins were tolerated after the age of 18 months in six children. Other atopic symptoms were observed in six children. CONCLUSION: Allergy to cow's milk protein hydrolysate is rare. The diagnosis is usually easy in children who develop acute anaphylactic symptoms, though intestinal histology is generally necessary for the diagnosis of allergy with chronic gastrointestinal symptoms. Treatment is based on the use of either another protein hydrolysate form (whey vs. casein) or an amino-acid-based formula.     

Educational clinical case series for pediatric allergy and immunology: Allergic proctocolitis, food protein-induced enterocolitis syndrome and allergic eosinophilic gastroenteritis with protein-losing gastroenteropathy as manifestations of non-IgE-mediated cow''s milk allergy

Cow's milk protein allergy is the most common food allergy in infants and young children. It is estimated that up to 50% of pediatric cow's milk allergy is non-IgE-mediated. Allergic proctocolitis is a benign disorder manifesting with blood-streaked stools in otherwise healthy-appearing infants who are breast- or formula-fed. Symptoms resolve within 48-72 h following elimination of dietary cow's milk protein. Most infants tolerate cow's milk by their first birthday. Food protein-induced enterocolitis syndrome presents in young formula-fed infants with chronic emesis, diarrhea, and failure to thrive. Reintroduction of cow's milk protein following a period of avoidance results in profuse, repetitive emesis within 2-3 h following ingestion; 20% of acute exposures may be associated with hypovolemic shock. Treatment of acute reactions is with vigorous hydration. Most children become tolerant with age; attempts of re-introduction of milk must be done under physician supervision and with secure i.v. access. Allergic eosinophilic gastroenteritis affects infants as well as older children and adolescents. Abdominal pain, emesis, diarrhea, failure to thrive, or weight loss are the most common symptoms. A subset of patients may develop protein-losing enteropathy. Fifty percent of affected children are atopic and have evidence of food-specific IgE antibody but skin prick tests and serum food-IgE levels correlate with response to elimination diet poorly. Elemental diet based on the amino-acid formula leads to resolutions of gastrointestinal eosinophilic inflammation typically within 6 wk.     

Cow's milk allergic patients should be informed of the sources of caseinate

Cow's milk allergy is one of the most common food allergies prevalent during infancy and it may cause anaphylactic reactions in more sensitive patients. Cow's milk is found in a large variety of processed foods but its presence may be hidden as it is occasionally listed on the product label in an manner unrecognizable to the consumer. The parents of more sensitive patients need to be instructed in the detection of these potential sources of hidden cow's milk by judiciously reading food labels and in recognition of the sources, thus avoiding possible untoward reactions. We report a patient with cow's milk allergy who had an anaphylactic reaction following the ingestion of a hot dog product that contained caseinate. The label of the ingested hot dog product listed only the code number of caseinate. Avoidance of such occurrences would be more likely if firstly food products were labeled more accurately and secondly if physicians were to instruct their patients more thoroughly about their allergies, including the relevant names of all allergens.     

Clinical and immunological aspects of food allergy in childhood. I. Estimation of IgG, IgA and IgE antibodies to food antigens in children with food allergy and atopic dermatitis

Sixtynine children with case histories of food intolerance and 30 food tolerant children with atopic dermatitis have been investigated regarding serum IgE levels and IgE-, IgG, and IgA-antibodies to some common foods. Children with food intolerance had significantly higher IgE levels and to a larger extent specific IgE antibodies to the tested allergens. IgE antibodies to cow's milk were found in 71% of the children with histories of cow's milk allergy but occurred also in similar titers in 27% of milk tolerant children with other food allergies. IgE antibodies to egg-white occurred in 88% of egg allergies, but low and moderate titers were also found in 17% of children without food intolerance. However, all children with high titers had symptoms of egg allergy. IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to the fish allergen were only found in fish allergic children while IgE antibodies to soy-bean and green peas were found less consistently. The level of serum IgA antibodies to milk was similar in both groups. The IgG antibody titers to all tested food antigens seemed to parallel the IgE antibody titer to the same food. It was not possible to correlate the IgG antibody titers to symptoms.     

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.     

The role of cow''s milk protein intolerance in steroid-resistant nephrotic syndrome

The role of cow's milk protein intolerance in steroid-resistant nephrotic syndrome was evaluated in 17 children. Cow's milk was excluded from the diet for at least 14 days without changing previously ineffective prednisone dosage. Six patients with minimal change or mesangial proliferation went into remission 3 to 8 days after elimination of cow's milk. After a period of 2-3 weeks of remission, cow's milk challenge was positive in three patients. After one year on a cow's milk-free diet, two of six patients became milk tolerant and are in remission of NS, one of six became steroid-dependent, two of six are still unable to tolerate cow's milk and are in remission on a cow's milk-free diet and one of six children was lost from observation. The role of cellular mechanisms in steroid-resistant nephrotic syndrome is suggested.     

Milk and soy allergy

Cow's milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of IgE and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle effect. It is logical that a review of CMA would be linked to a review of soy allergy because soy formula is often an alternative source of nutrition for infants who do not tolerate cow's milk. 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.     

Cow's milk allergy: guidelines for the diagnostic evaluation

About 2% of the general population and up to 6% of children suffer from food allergy. Cow's milk is charged with a important role in infancy after weaning, since conventional formula are based on its procession. IgE-mediated and Non-IgE- mediated allergic reactions, which are different in manifestation and pathogenesis, can be distinguished. A special role play the exacerbation of atopic dermatitis and the gastrointestinal-food-hypersensitivity-reactions. Skin-prick-test and determination of specific IgE are important diagnostic tools beside medical history. The golden standard of diagnosis is the double-blind-placebo-controlled-food- challenge. The clear result from food-challenge allows to verify suspected food allergies or, on the other hand, to avoid unnecessary diets. Extensively-hydrolysed-formula or Amino-acidformula are a high nutritional value alternative in case of proved cow's milk allergy in infancy.     

Anaphylaxis to sheep's milk cheese in a child unaffected by cow's milk protein allergy

A 5-year-old atopic boy unaffected by cow's milk protein allergy experienced several anaphylactic reactions after eating food containing “pecorino” cheese made from sheep's milk. Prick-prick tests were strongly positive to sheep's buttermilk curd and `pecorino' sheep's cheese. Skin prick tests to fresh sheep's milk and to goat's milk were also positive, whereas they were negative to all cow's milk proteins, to whole pasteurized cow's milk and to cheese made from cow's milk. Specific IgE antibodies were negative to all cow's milk proteins. Conclusion Sheep's milk and cheese derived from sheep's milk may cause severe allergic reactions in children affected and, as we report, in children not affected by cow's milk protein allergy. Received: 14 January 1997 and in revised form: 20 June 1997 / Accepted: 8 July 1997     

In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae

AIM: Because allergen-reduced formulae are widely used in the prevention and treatment of cow's milk allergy in children and because anaphylactic reactions have been reported for some hydrolysed formulae, it is of clinical relevance to know about the residual allergenicity of so-called hypoallergenic formulae. METHOD: We therefore studied the reactions of 20 children (mean age 1.6 years) with proven cow's milk allergy to a variety of formulae, using skin prick test, specific IgE in serum, protein content and RAST inhibition. RESULTS: Whereas all but two children with a clinically relevant cow's milk allergy had a positive skin prick test to cow's milk, some children still showed positive responses to the partially hydrolysed formulae. No child had a positive skin test to the amino acid formula. Specific IgE to the partially hydrolysed whey formula (median 0.28 U/ml) was significantly lower (p < 0.003) than to cow's milk. Specific IgE to the partially hydrolysed whey/casein formula, soy/pork collagen hydrolysate and the amino acid formula was in a low range (median values 0.19, 0.23 and 0.21 U/ml, respectively). While determination of the protein content of the formulae gave no valid information, RAST/EAST inhibition was highest for cow's milk, followed by the partially hydrolysed whey formula, partially hydrolysed whey/casein formula, soy/pork collagen formula, and the amino acid formula. CONCLUSION: Skin prick test and RAST inhibition test are suitable methods for determining the residual allergenicity of hydrolysed infant formulae, while determination of protein content using the applied modified Lowry method is not helpful.     

Efficacy of donkey's milk in treating highly problematic cow's milk allergic children: An in vivo and in vitro study

Successful therapy in cow's milk protein allergy rests on completely eliminating cow's milk proteins from the child's diet: it is thus necessary to provide a replacement food. This prospective study investigated tolerance of donkey's milk in a population of 46 selected children with cow's milk protein allergy, for whom it was not possible to use any cow's milk substitute. Thirty-eight children (82.6%) liked and tolerated donkey's milk at the challenge and for the entire duration of follow-up. Catch-up growth was observed in all subjects with growth deficit during cow's milk proteins challenge. The degree of cross-reactivity of immunoglobulin E (IgE) with donkey's milk proteins was very weak and aspecific. Donkey's milk was found to be a valid alternative to both IgE-mediated and non-IgE-mediated cow's milk proteins allergy, including in terms of palatability and weight-height gain.     

Formula feeding during cow's milk allergy

Cow's milk allergy (CMA) is an immunologically mediated reaction to cow's milk proteins, which affects infant and young children. Cow milk elimination requires either breast-feeding, with or without elimination diet in mother or the use of specific formulas, based on cow's milk protein extensively hydrolyzed, which fit 90-95% of children with cow's milk allergy. In others, still reactive to allergic remnants in hydrolysates, an amino acid based formula is the optimal option. The good tolerance of soy formulas in a reasonable proportion of children with cow's milk allergy make them useful, including as a 1(st)-choice alternative, except probably for those below the age of 6 months. Any elimination diet in children is at risk of nutritional deficiency so that a constant monitoring of the growth parameters should be kept in those children.     

Adverse reactions to milk in infants

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. CONCLUSION: Adverse 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.     

Correlation between skin prick test using commercial extract of cow''s milk protein and fresh milk and food challenges

The skin prick test (SPT) is regarded as an important diagnostic measure in the diagnostic work-up of cow's milk protein allergy. It is not known whether commercial extracts have any advantage over fresh milk. The aims of the study were to (i) compare the diagnostic capacity of SPTs for the three main cow's milk proteins (alpha-lactalbumin, casein and beta-lactoglobulin) with fresh milk and (ii) determine a cut-off that discriminates between allergic and tolerant children in a controlled food challenge. A study was carried out on 104 children consecutively attending two paediatric allergy clinics for suspected cow's milk allergy. A clinical history, SPTs with fresh cow's milk and commercial extracts of its three main proteins and a challenge test were performed on all the children. A study of the validity of the prick test was also performed by taking different cut-off points for fresh milk and its proteins. Twenty-eight of 104 challenge tests (26.9%) were positive. At a cut-off point of 3 mm, fresh milk showed the greatest negative predictive value (98%), whereas casein showed the greatest positive predictive value (PPV, 85%). Calculation of 95% predicted probabilities using logistic regression revealed predictive decision points of 12 mm for lactalbumin, 9 mm for casein, 10 mm for beta-lactoglobulin and 15 mm for fresh cow's milk. We found that the greater the number of positive SPTs for milk proteins, the more likely the positive response to challenge. Having a positive SPT for all three milk proteins had PPV of 92.3% and would seem more clinically useful than any cut-off. Both fresh milk and cow's milk extract of the three main proteins could be useful in the diagnostic work-up of cow's milk allergy. Finding positivity to all three cow's milk proteins seems to be a simpler and more useful way of avoiding oral food challenges.     

中国婴儿轻中度非IgE介导的牛奶蛋白过敏诊断和营养干预指南北大核心CSCD

牛奶蛋白过敏常见于婴幼儿,是由牛奶蛋白引起的异常免疫反应,发病机制可分为IgE或非IgE介导,亦或两者混合介导。目前我国已有多项牛奶蛋白过敏的专家共识,但这些共识均未对IgE和非IgE介导的牛奶蛋白过敏进行区分。鉴于两者在临床上有着明显不同,且婴儿时期非IgE介导的牛奶蛋白过敏更为常见,故中华预防医学会过敏病预防与控制专业委员会组织儿科消化、过敏/免疫、皮肤、营养和儿童保健专业专家,针对非IgE介导的牛奶蛋白过敏类型、临床特征、诊断和营养干预,参考国际指南并结合我国临床实践制定了本指南。本指南的建议更适合基层医师的理解和实践,涉及非IgE介导的牛奶蛋白过敏问题共7大类42条建议。     

A survey on clinical presentation and nutritional status of infants with suspected cow' milk allergy

Background  

Cow's milk is the most common food allergen in infants and the diagnosis of cow's milk allergy is difficult, even with the use of several diagnostic tests. Therefore, elimination diets and challenge tests are essential for the diagnosis and treatment of this disorder. The aim of this study is to report the clinical presentation and nutritional status of children evaluated by pediatric gastroenterologists for the assessment of symptoms suggestive of cow's milk allergy.