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Optimising the Approach to Cow's Milk Protein Allergy

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Optimising the Approach to Cow's Milk Protein Allergy Nestlé Nutrition Institute Symposium held at the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) meeting, Geneva, Switzerland Optimising the Approach to Cow’s Milk Protein Allergy The aim of this symposium was to gain a deeper understanding of food allergies, recognising the importance of reaching an early diagnosis, and considering the optimal management strategies that can be applied. The symposium also explored the role of the gut microbiota and its importance in the development of the immune system. State-of-the-Art in Food Allergy with Special IgE-mediated food allergy is the most common, and its diagnosis is straightforward as food-specific IgE testing or a skin prick test is typically Focus on Cow’s Milk Protein Allergy positive for immediate reactions. The best treatment is avoidance and self- administered epinephrine for emergencies. Professor Kirsi Järvinen-Seppo Division of Pediatric Allergy and Immunology and Center Diagnosis in non-IgE-mediated and mixed aetiology food allergies is not for Food Allergy, University of Rochester Medical Center, based on specific IgE. In allergic proctocolitis, blood streaked mucousy, loose Rochester, NY, USA stools appear up to six months of age in breast-fed or formula-fed infants who are otherwise well.5-7 The inflammation is eosinophil-dominant and cow’s Food allergy is an immune system-mediated adverse reaction, milk and soy are the most common triggers, although viruses can produce to food, which can be IgE-mediated, non-IgE-mediated or of mixed aetiology. a similar reaction. Bleeding resolves within three days following complete The IgE-mediated presentation is characterised by anaphylaxis, food- elimination of the allergen from the infant’s diet, and sometimes that of the dependent exercise-induced anaphylaxis, urticaria, angioedema, immediate mother. GI symptoms, bronchospasm and pollen food allergy syndrome. The non-IgE- Acute FPIES typically starts in early childhood and presents with emesis 2 to 4 mediated response is characterised by Coeliac disease, allergic proctocolitis hours after ingestion of the food protein, usually cow’s milk, soy, rice or oats. and food protein-induced enterocolitis (FPIES) all of which are commonly Diarrhoea may follow within 8 to 24 hours and there is often an appearance caused by cow’s milk. The mixed aetiology reactions typically present with eosinophilic oesophagitis or eosinophilic gastroenteritis, atopic dermatitis and of sepsis, with lethargy, limpness, and the risk of shock due to dehydration. asthma, commonly associated with consumption of cow’s milk. There is an increased white cell count, acidosis and methemoglobulinaemia in around 15% of cases. Around 6 to 8% of children are affected by food allergy, with cow’s milk, egg, and peanut being the most common. The prevalence of cow’s milk protein In chronic FPIES, which occurs earlier at around 1 to 3 months, there is allergy (CMPA) varies from 1 to 10% depending on the country or region,1,2 watery diarrhoea, failure to thrive, mucousy stools with intermittent emesis with self-reported allergy being up to four times as common as food-challenge associated with continuous exposure to cow’s milk, or soy formula. Blood confirmed allergy. The disparity between self-reported and confirmed food tests often reveal a low total protein. allergy is particularly noticeable for CMPA.3 Allergic eosinophilic gastroenteropathy affects either the oesophagus or the Children typically outgrow allergies to cow’s milk, egg, soy and wheat, lower GI tract. Allergic eosinophilic oesophagitis can present from infancy whereas allergy to peanuts, tree nuts, fish and shellfish typically persists until to adulthood with reflux symptoms, dysphagia, failure to thrive, irritability, adulthood, with a prevalence of about 3 to 4%. and vomiting. Allergic eosinophilic gastroenteritis generally appears up to adolescence and is characterised by vomiting, pain, anorexia, hematemesis, and even hypoalbuminaemia. The most common trigger for both is cow’s milk. Prevalence of Food Allergy At a molecular level, IgE-mediated allergy begins with digestion of the protein, followed by absorption and processing by antigen presenting cells before •Affects more than 1-2%, but less than 10%1-2 •Meta-analysis (EuroPrevall)3: presentation to T cells. The T cells, particularly Th2 type cells orchestrate Milk Egg Peanut Fish Shellfish the B cells to produce specific IgE antibodies to milk protein which are then bound by high affinity IgE receptors on mast cells. Upon re-exposure to the Self-reported 12-13% 3.5% 1% 0.75% 0.6% 1.1% same foods, parts of these allergens (epitopes) cross link consecutive IgE Symptomatic/sensitized 3% 0.6% 0.9% 0.75% 0.2% 0.6% molecules, resulting in the release of lipid mediators such as histamine and OFC-confirmed 3% 0.9% 0.3% n/a 0.3% n/a tryptase, which are responsible for the typical manifestations of flushing, vasodilation, pruritus, bronchoconstriction and vascular permeability. 1Chafen JAMA 2010, 2Sicherer JACI 1011, 3Rona et al JACI 2007 T cells also synthesise lipid mediators such as IL-4 which is responsible for The most important milk allergens are caseins and whey proteins, including mast cell up-regulation. IgA and IgG antibodies can suppress this reactivity ß-lactoglobulin and -lactalbumin. Most people with milk allergy are multi- by blocking antibodies and neutralising food antigens, and by T regulatory sensitised, and express IgE antibodies to a number of proteins. There is a high cells which suppress Th2 and mast cell activity. These molecules are key to level of cross-reactivity between the proteins of cow, goat and sheep milk, but developing tolerance to food allergens. 1 2 3 lessChafen so between JAMA 2010, cow, Sicherer camel, JACI and1011, pig Rona milk et al and JACI even 2007 less between cow, horse The non-IgE-mediated presentation has much more variable aetiology and is and donkey milk.4 not so well understood. Satellite Symposium Proceeding for ESPGHAN 2018 1 Geneva, May 11th, 2018 Food allergies are a growing clinical problem, with a doubling of peanut ESPGHAN guidelines for the diagnosis and management of CMPA26 cases in the US from 1997 to 2003, and a further doubling to 2008,8,9 and an 18% increase in all food allergies.10 There is similar data for Canada, United Kingdom, and Australia.11-13 The main increase is seen for peanut and tree nuts (three to four-fold), compared to a two-fold increase for milk and egg allergy. A 2016 paper proposed three different hypotheses to account for the increase in food allergy.14 One hypothesis suggests that reduced levels of vitamin D may be responsible for the development of more allergic diseases and asthma. The hygiene hypothesis proposes that exposure to a less diverse microbiological environment might induce intolerance to allergens. The dual allergen exposure hypothesis proposes that competing routes of exposure have opposite effects on the development of sensitisation and tolerance. Normal development of CD103+ dendritic cells induces tolerance in the GI tract, therefore most people become tolerant to ingested food through the development of T regulatory cells. However, skin allergen exposure can also contribute to sensitisation especially in those with filaggrin mutation, or significant eczema. Through daily exposure to food proteins, dendritic cells in questions on medical cases. people with abnormal skin barrier function, can up-regulate IL-4 cytokines in Over 2500 completed assessments were returned. There were more females the Th2 type memory. Although a person may rigorously avoid exposure via (72%), and the largest age group was 55 to 64 years, both of which are the oral route there can be continuing allergen exposure through the skin, representative of the respective societies. The majority, 72%, worked in which can be particularly sensitising when oral exposure is limited. paediatric practice, and had more than 20 years’ experience. There were Introduction of peanuts to the diet of high risk infants with significant eczema very few sub-specialists, only 4% were allergy specialists, so the majority can be a powerful tool for inducing tolerance.15 However, it is not known of responders would be the first point of contact for children suspected of whether the same applies to other food allergens. Most children who develop having a food allergy. CMPA also have eczema: if there is early introduction to the allergen in the first “In which circumstances would you switch a 3-month old formula-fed weeks of life this may help to develop tolerance. infant with suspected CMPA from a normal infant formula to a special There may be a window of opportunity that includes not just infant feeding therapeutic formula?” practices, decreasing C-sections and early life antibiotics, but also maternal exposure, environment, pets, lifestyle, diet, allergen and microbial exposures A number of possible responses were given and multiple answers were that can shape the immune system to become tolerant or sensitised.16 There allowed. is good data to suggest that farm life can protect from the development of Of the given options, failure to thrive (poor feeding, weight loss of 300g over asthma and allergic rhinitis. It is not clear whether this also protects from food the previous three weeks) was most appropriate to the guidelines and was allergy, although our work is continuing on this topic. selected by 53% of respondents. Forty-three percent also voted for moderate ß-lactoglobulin is found in very small concentrations in some women’s breast atopic eczema on the face and trunk. However, the most popular choice, 60%, milk, and is related to maternal diet.17-20 ß-lactoglobulin induces symptoms was blood-streaked stools for one week. such as eczema and rashes in some highly sensitised babies.20-22 When Rectal bleeding is an alarming symptom. However it is seen in breast-fed cow’s milk is eliminated from the mother’s diet, the eczema clears, while and non-breast-fed infants without any other signs of organic disease.27 re-exposure to milk protein through the maternal diet causes the rashes to Studies have found that in the majority of young infants, rectal bleeding is re-appear.
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