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.     

The spectrum of cow''s milk allergy

Childhood cow's milk allergy is a diagnosis encompassing various syndromes. Antigen-immunoglobulin E (IgE) antibody interaction is classically involved in mast cell degranulation in IgE-mediated food allergy, while non-IgE mediated cow's milk allergy is mostly mediated by cellular mechanisms. The diagnosis of cow's milk allergy largely relies on a good knowledge of the clinical expression of the disease. In this educational review series, we describe three cases of cow's milk allergy, first a 7-yr-old girl with persisting IgE-mediated cow's milk allergy, second a 8-month-old boy with cow's milk induced flares of atopic dermatitis, and third a 6-yr-old boy with sheep and goat milk allergy, in the absence of cow's milk allergy. The cases are discussed and summarized with more general recommendations for the clinical management of cow's milk allergy.     

Shellfish allergy in children

Food allergies affect approximately 3.5–4.0% of the world's population and can range from a mere inconvenience to a life-threatening condition. Over 90% of food allergies in childhood are caused by eight foods: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish, and shellfish. Shellfish allergy is known to be common and persistent in adults, and is an important cause of food induced anaphylaxis around the world for both children and adults. Most shellfish-allergic children have sensitivity to dust mite and cockroach allergens. Diagnostic cut-off levels for skin prick testing in children with shrimp allergy exist but there are no diagnostic serum-specific immunoglobulin E (IgE) values. All patients with symptoms of IgE-mediated reactions to shellfish should receive epinephrine autoinjectors, even if the initial symptoms are mild. In this study, we review three cases of clinical presentations of shellfish allergy in children.     

水解蛋白婴儿配方研究进展

牛奶过敏足婴幼儿最主要的食物过敏类型,1岁以内婴幼儿大约有2.5%的人群表现牛奶过敏.以天然牛奶蛋白为基础的水解蛋白配方,其变应原性降低,其中部分水解蛋白配方(pHF)可诱导口服免疫耐受,主要用于预防婴儿食物过敏和特应性皮炎;深度水解配方主要用于治疗婴儿牛奶过敏;严重牛奶过敏导致生长发育障碍的患儿,应用氨基酸配方治疗.     

Prevention and management of food allergy

The phenotypic expression and natural history of food allergy vary widely according to the patient's age, disease presentation and type of offending food. Prevention of food allergy might be achieved by altering the dietary factors responsible for the sensitization and phenotypic expression of the disease. Owing to the peculiarity of the atopic status, a minute amount of allergens can trigger both sensitization and symptoms in atopic individuals. The oral dose of β-lactoglobulin causing sensitization can be estimated to be between 1 ng and several milligrams. In food allergy, sensitization and treatment are allergen specific; therefore, for primary prevention (avoiding sensitization) and secondary prevention of food allergy (avoiding symptoms in an already sensitized subject), a product without immunogenic and allergenic epitopes should be given in each case. Babies of atopic parents are particularly prone to develop food allergy and for this reason they are called high-risk babies. Cow's milk is the most commonly offending food in both gastrointestinal and cutaneous manifestations. Cow's milk proteins are potent allergens and around 2.5% of infants experience cow's milk allergy in the first years of life. The major risk factors for cow's milk allergy are positive family history of atopy and early exposure to cow's milk proteins. Hydrolysate formulae have been developed for the purpose of reducing the allergenicity of cow's milk proteins. More recently, partially and extensively hydrolysed formulae have also been used for feeding babies with a high risk of atopy for the prevention of cow's milk allergy. However, according to the results of a recent randomized controlled study, only an extensively hydrolysated formula, and not a partially hydrolysated formula, significantly decreased the prevalence of cow's milk allergy.     

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.     

The Nutrition Committee of the Austrian Society of Pediatrics and Adolescent Medicine. Comment on nutrition with solid foods in infancy and early childhood]

The Nutrition Committee of the Austrian Pediatric Society recommends that weaning foods should be introduced between 4 and 6 months of age, which agrees with the recommendations in the EC and the U.S. Opinion against early introduction of solid foods have focused on concerns about renal solute load, obesity, coeliac disease, and food allergy. On the other hand, when weaning was postponed after 6 months of age, growth faltering in some breastfed infants and iron-deficiency anemia in infants fed non-fortified formulas or cow's milk were observed. Two broad categories--"baby foods" and "cereal-based weaning foods"--are on the market in Austria. "Baby foods" include complete meals sold in jars, soups, desserts and puddings, fruit juices, nectars, and vegetable juices. "Cereal-based weaning foods" are composed of one or more cereals either alone, or with the addition of vegetables, fruits, milk and milk products, egg, or other ingredients. Weaning food labelling should include information if sugars, salt, iron, vitamins minerals and trace elements have been added and if the product is free from gluten, cow's milk and egg protein, and lactose.     

水解蛋白配方与婴幼儿牛奶过敏的预防和治疗

食物过敏是婴幼儿最早出现的过敏问题,牛奶是婴幼儿最常见的过敏食物。牛奶过敏的临床表现多种多样,可涉及皮肤、呼吸道、消化道等多器官多系统。母乳喂养是过敏高风险婴儿的首选喂养方式,但对不能进行母乳喂养的婴儿应选择适当的低敏配方奶,水解蛋白是获得低敏配方的最好方法。根据水解的程度,水解蛋白配方分为适度水解蛋白配方和完全水解蛋白配方。完全水解配方被推荐用于牛乳蛋白过敏婴儿的治疗,适度水解配方通常推荐用于特应质高风险婴儿的初级干预。     

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.     

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.     

婴儿期食物过敏的预后研究

目的了解婴儿期食物过敏（FA）的预后及影响因素。方法对119例患儿进行回顾性研究,采用Kaplan-Meier法计算食物耐受的累积概率,非条件Logistic回归模型分析食物耐受形成的预测因素和其他过敏性疾病发生的影响因素。结果鸡蛋、牛奶耐受的累计概率在诊断后1年分别为31％、42％;2年为62％、63％;3年为80％、77％;4年后均可达100％。牛奶、鸡蛋过敏患儿的皮肤点刺试验阳性强度是持续牛奶、鸡蛋敏感的预测因素（OR=2．535,95％CI：1．159～5．543;OR=2．654,95％CI：1．302～5．410,P均〈0．05）。本组13例患儿发生其他FA,危险因素是持续鸡蛋敏感（OR=6．109,95％CI：1．818～20．527,P〈0．05）;4例发生变态反应性鼻炎,15例发生支气管哮喘,危险因素是持续鸡蛋敏感和呼吸道过敏症状（OR=3．596,95％CI：1．429～9．045;OR：4．235,95％CI：1．152～15．563,P均〈0．05）。结论至少75％的鸡蛋或牛奶过敏患儿在诊断后3年内可获耐受。10．9％、12．6％和3．4％的FA儿童发生其他FA、支气管哮喘和变态反应性鼻炎。加强持续FA高危儿的筛查和管理,可能有助于改善FA的预后。     

Skin prick test predictive value on the outcome of a first known egg exposure in milk-allergic children

Children with milk allergy have higher incidence of other food allergies, especially egg allergy. The objective of this study was to ascertain the accuracy of the prick test in children with IgE-mediated milk allergy for diagnosing egg allergy. Children under the age of 1 yr who came consecutively to Allergy Department 2003–05, and were diagnosed with IgE-mediated milk allergy were selected for this study. Egg introduction was completely avoided until the age of 14 months when clinical history, skin prick tests (SPT), specific-IgE antibodies determination and egg challenge test were performed. One hundred and four milk-allergic children were included. At least one positive prick test to any egg allergen was found in 65 out of the 104 (62.5%). Thirty-eight (36.5%) were allergic to egg proteins as well. Prick tests with egg white and ovomucoid (OVM) had the best diagnostic performances showing the largest areas under the receiver operating characteristic curve. The optimal diagnosis cut-off point was 6 mm for egg white and 5 mm for OVM. The positive likelihood ratios for these cut-off points were: 2.95 (95% CI: 1.74–4.99) for egg white prick test, and 20 (95% CI: 2.9–143.7) for OVM prick test. Children with specific IgE-mediated cow's milk allergy must be closely followed as a risk group for egg allergy. Early diagnosis is necessary and the SPT has shown itself to be a very useful tool for diagnosing immediate IgE reactions to egg on first known exposure.     

Epidemiology of food allergy

Food allergy (FA) is perceived as a common problem, especially during childhood. Accurate assessment of incidence and prevalence of FA has been difficult to establish, however, due to lack of universally accepted diagnostic criteria. Although many foods are reported to cause IgE-mediated FA, most studies focus on 4 common food groups: cow's milk, hen's egg, peanut/tree nuts, and fish/shellfish. There may be variation in the prevalence of FA in regions of the world and a likely increase in prevalence has been observed in recent decades. This cannot be stated with confidence, however, without the use of consistent methodology and diagnostic criteria.     

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     

Breast feeding and the dietary habits of children in rural Somalia

Breast feeding and dietary habits were studied prospectively in a cohort of children under the age of five years in a rural Somali community. The median duration of breast feeding was 19.5 months. However, all the children also received cow's milk by cup from the first day of life and onwards. Energy supplements (mainly sugar and oil) as well as additional water were given daily from early infancy. Staples, protein-rich foods (beans and meat), vegetables and fruits were usually introduced when the children reached the age of 12-18 months. There was a seasonal variation with the lowest intake of protein-rich and vitamin-rich foods during the rains in May to June. Thus, there was a complete absence of exclusive breast feeding. Energy-reinforced cow's milk and human milk dominated the diet up to the age of one year. Staples were mixed with oil and supplemented with milk, thereby leading to a much higher energy density in the complementary food than is usually the case in African communities.     

Parent-reported food allergy requiring an avoidance diet in children starting elementary school

Aim: To evaluate the prevalence of parent‐reported food allergies requiring avoidance diet at early school age. Methods: The school health nurses interviewed, by using a structured questionnaire on the required diet at school, the parents of all the 1542 children starting elementary school in a Finnish town with 210 000 inhabitants. Results: An allergy to basic foods was found in 41 (2.7%) children: 1.5% to milk, 1.1% to eggs and 1.0% to grains. An allergy to nuts was present in 3.1% and to fruits and vegetables in 5.8%, both with known cross‐sensitization to pollens. In all, 9.2% of the children reported some allergy. Milk, egg and grain allergies were associated with soy, nut and spice allergies. Conclusion: Over 2% of the 1542 Finnish first‐graders reported allergies to basic foods (milk, eggs or grains) requiring special avoidance diets at school. The figure suggests that avoidance diets started in the first years of life still unnecessarily continued.     

Milk allergy school: Nutritional therapy in group for parents of children with cow''s milk allergy/intolerance in Primary Health Care

The objective of this study was to create a method for group nutritional therapy for parents of children with cow's milk allergy/intolerance in a paediatric primary care setting to increase accessibility to nutritional therapy. A second objective was to evaluate a milk allergy school. Follow-up time after the group session was 3 yr. All parents to newly diagnosed children (n=98) with cow's milk allergy/intolerance in the Primary Health Care system in the city of Goteborg during an 11-month period were invited. The majority of the families chose to participate (n=84, 86%). The mean age of the children was 9 months (3 months to 5 yr). The number of participants obtaining nutritional treatment within a month after diagnosis has significantly increased. Seventy-four families (88%) could be re-contacted 3 yr after participation for a second evaluation. Seventy-eight per cent of the children no longer had cow's milk allergy/intolerance. Most participants expressed satisfaction with the information obtained in the meeting. The milk allergy school does not replace but complements individual counselling. The milk allergy school seems to meet the families' needs for information, has few administrative routines and is cost-efficient. This activity has become permanent, is being offered weekly and can be recommended.     

Food protein-induced enterocolitis syndrome – not only due to cow's milk and soy

Over a of 7-year period, six patients (four males, two females aged 3–12 months) were diagnosed with food protein-induced enterocolitis syndrome (FPIES) triggered by foods other than cow's milk and soy: chicken in four, turkey in two, peas in one, and lentils in one (five patients reacted to more than one food type). All reactions developed within 2 h of ingestion of the allergenic food. To exclude other conditions with similar clinical symptoms, three infants underwent work-up for sepsis, one infant underwent work-up to exclude metabolic defects, and one underwent a barium enema to rule out intussusception. All were negative. Pediatricians should be aware that FPIES may be caused by foods other than cow's milk and soy, mainly chicken, turkey and foods from the legume family, and that it may present also in infants older than 6 months.     

三城市两岁以下儿童食物过敏现状调查

目的 通过多中心大样本研究了解我国0～2岁儿童食物过敏现状.方法 将2009年1月至2月及2010年1月至5月在重庆、珠海、杭州3城市儿童保健机构进行常规体检的儿童依次纳入研究.家长填写问卷调查表,对所有纳入儿童进行皮肤点刺试验,筛查的10种食物抗原提取物,包括蛋白、蛋黄、牛奶、大豆、花生、小麦、鱼(海鱼)、虾(海虾)、橘子和胡萝卜.根据皮肤点刺试验和病史结果确定的可疑病例进行食物排除和食物激发试验,按激发试验结果确诊食物过敏.结果 3城市1687例0～2岁儿童中除83例失访外,共有1604例儿童(重庆550例,珠海573例,杭州481例)完成诊断过程.食物激发试验确诊食物过敏儿童100例(重庆40例,珠海33例,杭州27例).重庆、珠海、杭州儿童食物过敏检出率分别为7.3％,5.8％,5.6％,3城市儿童食物过敏平均检出率为6.2％,3城市间儿童食物过敏检出率差异无统计学意义(x2=1.058,P=0.304);最常见的食物过敏原均为鸡蛋(3.0％～4.4％),其次是牛奶(0.83％～3.5％)、虾(0.17％～0.42％)、鱼(0.17％ ～0.21％).结论我国3城市0～2岁儿童食物过敏检出率为5.6％ ～ 7.3％;3城市间儿童食物过敏检出率相近;最常见的食物过敏原为鸡蛋,其次是牛奶、虾和鱼.     

Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis

Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulae (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino-acid-based formulae (AA) in such infants. We therefore performed a prospective, controlled, multi-center trial to study the efficacy of AA in comparison with eHF, on the growth and clinical symptoms of 73 infants (median age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's milk allergy/intolerance was proven in all infants by double-blind, placebo-controlled food-challenge. We observed a significant improvement in the SCORAD index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p < 0.0001) after 6 months. In the AA group there was a significant increase in the length standard deviation score (p < 0.04), whilst there was no difference in the eHF group. The weight-for-length values were stable in both groups. The energy intake during the study was similar in both groups. Both an AA and eHF resulted in a significant clinical improvement in infants with an early onset of symptoms of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth compared with feeding eHF, despite similar dietary intakes, and may therefore be considered as a beneficial alternative in infants with severe cow's milk allergy intolerance.