The pendulum between food protein-induced enterocolitis syndrome and IgE-mediated milk allergy

The transition from milk protein-induced enterocolitis syndrome to IgE-mediated milk allergy is uncommon. Herein, we describe three infants that suffered from recurrent vomiting and restlessness in response to cow's milk formula with negative skin prick to milk and therefore diagnosed as milk protein-induced enterocolitis syndrome. After recovering and reintroducing cow's milk formula, they developed disseminated urticaria and positive skin prick test to cow milk compatible with IgE-mediated milk allergy. CONCLUSION: An infant that recovers from cow milk food-induced enterocolitis syndrome might develop afterward IgE-mediated cow 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.     

Cow's milk protein allergy and gastro-oesophageal reflux

Evidence for cow's milk allergy was looked for prospectively in 15 children with recurrent vomiting. Whereas radiological examination showed gastro-oesophageal reflux to be present in all patients, 3 out of 15 children presented an enteropathy associated with an increased number of IgE plasmocytes in small intestinal biopsy tissue. These three patients did not improve with conventional medical therapy but a striking improvement occurred within 24 h on a cow's milk-free diet. We conclude that diagnostic confusion between gastrooesophageal reflux and cow's milk allergy can occur and that the presence of IgE plasmocytes in small intestinal biopsy tissue indicates IgE-mediated cow's milk protein allergy. All cases of intractable gastro-oesophageal reflux should be suspected of cow's milk allergy and investigated acrodingly.Abbreviation GER gastro-oesophageal reflux     

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.     

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     

Immunologic disturbances in cow's milk allergy, 1: delayed maturation of suppressor activity

To assist in identifying pathogenetic mechanisms in different subtypes of cow's milk allergy (CMA), the function of immunoregulatory T-lymphocytes was studied. The study population consisted of 23 patients, mean [95% confidence interval] age of 25. 6 [19. 5, 33. 6] months, who had challenge-proven cow's milk allergy manifested with either skin (n=9) or gastrointestinal (n=14) symptoms; in addition, 13 age-matched disease controls were studied. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The suppressor activity of isolated lymphocytes was measured in vitro by a cell coculture at rechallenge and in 10/23 patients at diagnosis. At diagnosis, patients with CMA (n=10) showed a decreased mean [95% CI] suppressor activity, induced by either Concanavalin A, 7[-2, 15]%, or cow's milk, 3[-8, 14]% as compared with disease controls (n = 13), 19[15, 24]% and 24[17, 31]%; F = 7. 1, p = 0.004 and F = 6. 7, p = 0.005, respectively. At rechallenge the suppressor activity, induced both by Concanavalin A and cow's milk, reached the level of disease controls only in patients who had acquired clinical tolerance to cow's milk (n = 13/23), but not in those retaining CMA (n = 10/23). Our results indicate that the maturation of suppressor function is delayed in CMA, which might be of primary importance in the etiopathogenesis of CMA.     

Cows milk protein enteropathy and granulomatous duodenitis in a newborn

Cow's milk protein enteropathy is a symptom complex that composed of severe diarrhoea and malnutrition. This disorder is caused by non-immunoglobulin E-mediated food allergy. Its clinical features and natural course have been explained in many reports, of different types of cow's milk and soy reactions. In the present article, we describe a newborn patient who presented with chronic diarrhoea and failure to thrive diagnosed as cow's milk protein enteropathy. The duodenal biopsy revealed granulomatous duodenitis which has not been described before. Her clinical and pathological findings responded well to cow's milk elimination. We suggest that food allergies should be considered in differential diagnosis of patients with chronic diarrhoea and failure to thrive.     

Food allergy as a risk factor for nutritional rickets

The case of a 14-month-old boy with vitamin D deficiency rickets as a result of unsupervised dietary manipulation in the context of cow's milk allergy is presented. Adequate supervision by a qualified dietician, coupled with appropriate supplementation, is essential if nutritional compromise is to be avoided in children with food allergy.     

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.     

Anaphylactic reaction to goat's milk in a cow's milk-allergic infant

Goat's milk has been used as a substitute for cow's milk in cow's milk-allergic individuals. It is currently advocated for this purpose in writings and internet resources directed at the lay person, and infant formula based on goat's milk is available in many countries. Clinically significant cross-allergenicity between cow's and goat's milk has been noted, but a life-threatening cross-reaction has not been reported. We describe a 4-month-old infant with immunologically documented cow's milk protein allergy but no prior exposure to goat's milk who developed anaphylaxis after the ingestion of commercial goat's milk. Subsequent skin prick testing demonstrated a specific reaction to goat's milk. Thus, the cross-allergenicity between cow's and goat's milk proteins can lead to life-threatening complications. Individuals allergic to cow's milk protein should avoid goat's milk and goat's milk products.     

A case of cow's milk allergy in the neonatal period-evidence for intrauterine sensitization?

Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic mecon-ium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevaled total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy— induced by intrauterine sensiti-zation—explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra-uterine sensitization to allergens.     

A FOLLOW-UP STUDY OF INFANTS WITH ADVERSE REACTIONS TO COW'S MILK I. Serum IgE, Skin Test Reactions and RAST in Relation to Clinical Course

Abstract. 47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

Immunologic disturbances in cow's milk allergy, 2: evidence for defective interferon-gamma generation

We have investigated the role of interferon-gamma (IFN-gamma) in the regulation of antigen-specific T-cell function in patients with cow's milk allergy. The study population consisted of 22 patients, aged from 7. 6 to 56. 9 months, who had challenge-proven cow's milk allergy (CMA) manifested with either skin (n=9) or gastrointestinal (n=13) symptoms. In addition, 11 age-matched children and 6 adults, mean (SD) age 31 (7) years, were studied as controls. Patients with challenge-proven CMA were rechallenged to establish whether they had acquired clinical tolerance to cow's milk. The spontaneous and mitogen-induced IFN-gamma and interleukin-4 (IL-4) generation of isolated lymphocytes was evaluated in vitro with commercial ELISA Kits at diagnosis and at reassessment. At diagnosis, the IFN-gamma production was not detectable in patients with CMA as compared with control children. IL-4 production was almost undetectable in all subjects in this study. However, at reassessment the CMA patients who had acquired clinical tolerance to cow's milk (n=16) showed enhanced IFN-gamma production, when compared with that of control children, but still lower when compared with that of healthy adults. Our results indicate that the maturation of IFN-gamma producing T-cells is delayed in CMA, which could lead to a disturbance in the regulation of T-cell function. This defect might be an important etiologic factor for CMA.     

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.     

Low Colostral IgA Associated with Cow's Milk Allergy

ABSTRACT. During a nutritional study of 198 infants, seven became allergic to cow's milk. The seven infants showed acute cutaneous manifestations during cow's milk challenge tests in hospital and six had increased levels of IgE cow's milk-specific antibodies. Neither in the development of the levels of immunoglobulins G, A and M, nor in that of the cow's milk-specific antibodies of these isotypes did these seven patients differ from the remaining infants. Beta-lactoglobulin content and levels of cow's milk-, and beta-lactoglobulin-specific antibodies and of immunoglobulins A, G and M were measured in samples of colostrum and milk from the mothers of the seven infants with cow's milk allergy and from a comparison group (non-atopic mothers of non-atopic infants). The milk of the mothers whose infants became allergic to cow's milk contained less IgA through the lactation: 95% confidence intervals of the groups did not overlap. The difference was most marked in the colostrum. All other measurements were similar in the two groups. This suggests that an infant is more likely to develop cow's milk allergy if the mother's colostrum had a low total IgA content.     

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.     

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。     

Lymphocyte response to cow's milk proteins in patients with cow's milk allergy: relationship to antigen exposure

The cellular immune response to cow's milk was measured in patients with challenge-proven cow's milk allergy (CMA), manifested with either gastrointestinal or skin symptoms. After 2–4 weeks on milk elimination, 44 children, mean (SD) age 15.7 (9.4) months, were challenged, and cow's milk-induced lymphocyte transformation was measured before the clinical challenge (Day 1) and / or one week later (Day 8). During the clinical challenge period, 17 (39%) patients showed gastrointestinal reactions, 9 (20%) had urticarial or eczematous skin eruptions, and 18 (41%) were negative to challenge. On Day 1, the mean [95% confidence interval] stimulation index for lymphocytes in patients manifesting CMA with gastrointestinal symptoms, 2.60 [1.60, 4.10], was significantly higher than that in patients with skin symptoms, 1.15 [0.60, 2.30], or patients with negative clinical challenge, 0.83 [0.64, 1.08], F = 9.0, p = 0.001. After the clinical challenge (Day 8), this cow's milk-induced lymphocyte proliferation response was abrogated. At the same time, CMA patients evidenced a significantly higher spontaneous lymphocyte proliferation response in RPMI medium-containing control cultures than those with negative clinical challenge. We conclude that in patients with CMA, the number of circulating cow's milk-sensitized lymphocytes is depleted or their function is impaired after clinical exposure to cow's milk antigens.     

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.     

Frequency of food allergy in a pediatric population from Spain

We evaluated the prevalence and characteristics of the principal foods implicated in 355 children diagnosed with IgE-mediated food allergy. Diagnosis was established on the basis of positive clinical history for the offending food, positive specific IgE by skin prick test and RAST, and open food challenge. Our results showed the principal foods involved in allergic reactions are: eggs, fish, and cow's milk. These are followed in frequency by fruits (peaches, hazelnuts and walnuts), legumes (lentils, peanuts and chick peas) and other vegetables (mainly sunflower seeds). The legumes demonstrated the highest degree of clinical cross-reactivity. Most patients with food allergy reacted to one or two foods (86.7%). Only 13.3% of patients reacted to 3 or more foods, mostly to legumes and fruits. We found that food allergy begins most frequently in the first (48.8%) and second (20.4%) years of life. Allergy to proteins of cow's milk, egg, and fish begins predominantly before the second year, demonstrating a clear relationship with the introduction of these foods into the child's diet. Allergy to foods of vegetable origin (fruits, legumes and other vegetables) begins predominantly after the second year.;