Use of an amino-acid-based formula in the treatment of cow's milk protein allergy and multiple food allergy syndrome

Food allergy to cow's milk proteins (APLV) is frequently found in young infants. Treatment is by starting an elimination diet. Different substitution products have been proposed: soya milk, partial hydrolysate of the proteins of lactoserum, powdered casein hydrolysate, hydrolysed soya and pork collagen. Allergic reactions to soya milk, hydrolysates of lactoserum proteins, powdered casein hydrolysates and hydrolysates of soya have been described. The study that we present evaluates the effect on the natural development of these allergies of a formula based on amino-acids (Neocate) in 26 patients who presented a syndrome of multiple allergies one of which was a food allergy to milk. Twenty-five of them had a severe atopic dermatitis, isolated (14 cases), or associated with gastro-intestinal troubles (6) break in the growth curve (5), anaphylactic reactions (2), one asthma (1). One child had a chronic diarrhoea associated with a weight plateau. Evaluation 2 or 3 months later showed a significant improvement of the atopic dermatitis. Return of the stature-weight growth was noted in 4 children from 5, the check in one was reported as due to a initially unrecognised allergy to gluten. The recovery of the APLV was shown by double-blind oral provocation test in 20/23 children between 11 and 37 months (22 +/- 9). Duration of administration of Neonate was between 6 to 19 months (12 + 5) months. This study confirmed the beneficial effect of the amino-acid formula on weight gain, gastro-intestinal troubles and development of atopic dermatitis. The level of recovery of APLV of 86% at the age of 2 years is better than that reported in the syndrome of multiple food allergies of 22%. The influence of this diet on the development of other food allergies remains to be evaluated.     

Japanese guidelines for food allergy 2020

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.     

Japanese guidelines for food allergy 2017

Five years have passed since the Japanese Pediatric Guideline for Food Allergy (JPGFA) was first revised in 2011 from its original version. As many scientific papers related to food allergy have been published during the last 5 years, the second major revision of the JPGFA was carried out in 2016. In this guideline, food allergies are generally classified into four clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type of food allergy (urticaria, anaphylaxis, etc.), and (4) special forms of immediate-type of food allergy such as food-dependent exercise-induced anaphylaxis and oral allergy syndrome (OAS). Much of this guideline covers the immediate-type of food allergy that is seen during childhood to adolescence. Infantile atopic dermatitis associated with food allergy type is especially important as the onset of most food allergies occurs during infancy. We have discussed the neonatal and infantile gastrointestinal allergy and special forms of immediate type food allergy types separately. Diagnostic procedures are highlighted, such as probability curves and component-resolved diagnosis, including the recent advancement utilizing antigen-specific IgE. The oral food challenge using a stepwise approach is recommended to avoid complete elimination of causative foods. Although oral immunotherapy (OIT) has not been approved as a routine treatment by nationwide insurance, we included a chapter for OIT, focusing on efficacy and problems. Prevention of food allergy is currently the focus of interest, and many changes were made based on recent evidence. Finally, the contraindication between adrenaline and antipsychotic drugs in Japan was discussed among related medical societies, and we reached an agreement that the use of adrenaline can be allowed based on the physician's discretion. In conclusion, this guideline encourages physicians to follow the principle to let patients consume causative foods in any way and as early as possible.     

Aliments et dermatite atopique

Food allergy plays a pathogenetic role in subset of patient with atopic dermatitis, as proven over the past decade by laboratory and clinical investigations. Likely 40% of infants and young children may present with food allergy, whatever the severity of atopic dermatitis. The identification of the subset of patient with relevant food allergy requires a thorough a clinical history, the appropriate laboratory tests, food allergy being proven in all cases by elimination diets followed by provocation tests. Atopic dermatitis may be cured or largely improved by elimination diets, but the latter need a peculiar education of patient and physicians because the common causal foods involved (egg, milk, wheat, soil, peanut) are ubiquitous in industrial foods and since elimination diets are at risk of nutritional imbalances. Most food allergies resolve following early childhood and atopic dermatitis in older children and adults is largely less related to food allergy.     

Japanese Guideline for Food Allergy 2014

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food."Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy).The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.     

Définitions des termes utilisés en allergologie alimentaire chez l’enfant

In so far as there are no recent medical references that specify terms used in allergy, and particularly terms dealing with food allergy, it seemed to us that it would be of use to compile a glossary that would be helpful in daily practice. The defined terms (plus comments) have been retained according to sequences that correspond to steps in a food allergy work-up. The following terms are entered successively in this review: atopic dermatitis; SCORAD; asthma; pulmonary function tests; medications for children; symptoms and severity of food allergies; immediate skin tests; intradermal tests or “atopy patch-tests”; allergen-specific and total serum IgE levels; oral provocation test; labial provocation test; other tests used in allergy work-ups; allergy, hypersensitivity, atopy; allergens, allergies, sensitizations, allergic cross-reactions; treatment of an allergic reaction.     

From atopic dermatitis to asthma: the natural history of allergy

The natural history of allergy is a medical reality : children suffering from moderate to severe atopic dermatitis often become older asthmatic children. The severity of the cutaneous lesions and the appearance of sensitizations (often food allergies) before the 2 years of age are predictive risk factors of a later asthma in these children. There is no validated primary prevention available, apart from passive tobacco smoke avoidance. Conversely, allergic patients with demonstrated sensitizations should benefit from specific avoidance procedures.     

Phenotypes of IgE-mediated food allergy in Turkish children

Data on food allergy-related comorbid diseases and the knowledge on factors associating specific food types with specific allergic outcomes are limited. The aim of this study was to determine the clinical spectrum of IgE-dependent food allergy and the specific food-related phenotypes in a group of children with IgE-mediated food allergy. Children diagnosed with IgE-mediated food allergy were included in a cross-sectional study. IgE-mediated food allergy was diagnosed in the presence of specific IgE or skin-prick test and a consistent and clear-cut history of food-related symptoms or positive open provocation test. Egg (57.8%), cow's milk (55.9%), hazelnut (21.9%), peanut (11.7%), walnut (7.6%), lentil (7.0%), wheat (5.7%), and beef (5.7%) were the most common food allergies in children with food allergy. The respiratory symptoms and pollen sensitization were more frequent in children with isolated tree nuts-peanut allergy compared with those with egg or milk allergy (p < 0.001); whereas atopic dermatitis was more frequent in children with isolated egg allergy compared with those with isolated cow's milk and tree nuts-peanut allergy (p < 0.001). Children with food allergy were 3.1 (p = 0.003) and 2.3 (p = 0.003) times more likely to have asthma in the presence of allergic rhinitis and tree nuts-peanut allergy, respectively. Interestingly, children with atopic dermatitis were 0.5 (p = 0.005) times less likely to have asthma. Asthma (odds ratio [OR], 2.3; p = 0.002) and having multiple food allergies (OR, 5.4; p < 0.001) were significant risk factors for anaphylaxis. The phenotypes of IgE-mediated food allergy are highly heterogeneous and some clinical phenotypes may be associated with the specific type of food and the number of food allergies.     

What are the links between food allergy and atopy ?

Food allergy and atopy are closely linked. In children, food allergy is often the first clinical manifestation of atopy and involved in flares of atopic dermatitis. It is usually disappearing with ageing except for some particular allergens. Asthma and/or allergic rhinitis might develop later particularly if there are some risk factors as familial history of atopy or sensitization to aeroallergens. However some food allergies as allergy to peanut or tree nuts may persist in adulthood sometimes inducing severe clinical manifestations especially in asthmatic patients. In adult, food allergy is mostly associated with oral syndrome linked to cross reactivity between pollen and raw food (fruits or vegetables). Systemic manifestations are more frequent in patients living in the Mediterranean area in relation to direct sensitization (without pollen allergy) to lipid transfer proteins that are particularly resistant.     

Patch tests in the diagnosis of food allergies in the nursing infant

The atopy patch-test has been shown to be useful in diagnosis of delayed reactions in infants with atopic dermatitis or digestive symptoms. The combination of skin prick testing and patch testing can significantly enhance the accuracy in diagnosis of specific food allergy in infants with atopic dermatitis or digestive symptoms.     

Etiologic implication of foods in atopic dermatitis: evidence against

Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.     

Risk of allergy to food proteins in topical medicinal agents and cosmetics

The risk of allergy to food proteins in cosmetics and topical medicinal agents is poorly evaluated. IgE dependent contact urticaria and contact dermatitis are observed. Eleven cases (7 infants and 4 women) are reported. Wheat, egg, oats, milk, peanut proteins are incriminated by prick-tests or atopy patch-tests. Cases are related to a previous food allergy and other ones may indicate primary sensitization to topical creams mainly used for skin care of atopic dermatitis. A consecutive exercise induced anaphylaxis to wheat and a long lasting sensitization to wheat have been observed. A clear and accurate identification of food allergens in cosmetics and topical agents is necessary. Given the hyper-permeability of infant skin, topical products containing food proteins of known allergenicity are contra-indicated for neonates, and for infants with atopic dermatitis, which may be associated with skin hyper-permeability.     

Dermatite atopique et allergie alimentaire chez l'enfant

Food allergy is known to provoke flares of atopic dermatitis (AD). The prevalence of food allergy in infants with atopic dermatis has been estimated to be 40%. Atopy patch testing is a novel approach to diagnose food-induced AD, but standardization of atopy patch test extracts needs addional studies. Oral food challenge is the gold standard for diagnose of food allergy. Nevertheless, the method used for oral food challenges in cases of late eczematous reactions remains to be defined. Food appears to aggrevate eczematous lesions in young children, and it is recognized that allergy testing needs to be standardized in order to prove that relationship.     

Quoi de neuf en allergologie pédiatrique en 2000 ?Revue de la littérature internationale dˈoctobre 1999 à octobre 2000

The relation between maternal and childhood atopy may result from an increased intrauterine Th2 environment and high levels of Th2 cytokines in the milk of atopic mothers. The value of in vitro tests for early prediction of atopy is low, but high levels of eosinophil-derived proteins in nasal secretions of neonates may predict respiratory allergy. The prevalence of respiratory allergy has decreased in children living in rural areas, especially on farms. This may be related to exposure to mycobacterias, but the development of allergic conditions is independent of tuberculin reactivity and history of tuberculosis infection; however, the prevalence of asthma is decreased in young adults infected by Mycobacterium tuberculosis during childhood. High levels of eosinophils in the blood of children with bronchiolitis predict the development of persistent wheezing and asthma. Inhaled, oral and intravenous corticosteroids do not prevent relapses of bronchiolitis and persistent wheezing, but early hyposensitization has long-term beneficial effects on asthmatic symptoms. Results of prick-tests and specific IgE determinations are correlated with the severity of food allergy, and several studies confirm the diagnostic value of patch-tests with foods in children with atopic dermatitis associated with food allergy. Interesting cases of unexpected food allergies are reported (carob-induced anaphylaxis, and exercise-induced anaphylaxis to snails). Finally, children with spina bifida demonstrate a progressive sensitization to latex, in spite of a latex-free environment after the first surgical procedure(s), and the gelatin included in vaccines is highly immunogenic and allergenic.     

The growing genetic links and the early onset of atopic diseases in children stress the unique role of the atopic march: a meta-analysis.

Allergic asthma and rhinitis, atopic dermatitis, urticaria and food allergy are genetic diseases present in infants and children. Several investigators have provided evidence for a genetic localization for atopy. Babies of atopic parents are at high risk of developing atopic diseases; however, the phenotypic expression of such diseases varies widely in that it can be very mild in some infants and children, severe and frustrating in many, even life-threatening in others, as well as also being common, disabling and chronic. A meta-analysis of all available studies on the age of onset of atopic march was carried out by selecting what appeared to be the most relevant articles in the literature rather than aiming for a comprehensive selection. It was found that in the first year of life, there is the onset of atopic dermatitis in 79.8% (60.2-100%) of babies, of cow's milk allergy in 72.7%, egg allergy in 71%, and fish allergy in 51.3%. Asthma starts in the first year of life in 41.8%, in the second in 49.3%, and within the eighth year in 92.5% of children. Allergic rhinitis begins in 35% of babies in the first year of life, and in 59% or 13-19% in those aged 2-5 years. It seems therefore that up until now the role of pediatric allergy and immunology has been somewhat obscured, as can be witnessed by atopic march. Instead, pediatric allergy and immunology have a substantial, unmatched role, focusing on the early and often very early onset of atopy, which requires strategic intervention in the very first months of life or even before birth. As the main goal of modern medicine is prevention of chronic and severe diseases, the possibility of preventing such disorders in predisposed children has stimulated the imagination of researchers since the beginning of the century, when atopic diseases were not as common as they are now.     

Prevention of allergic diseases

The prevalence of asthma and allergic diseases has increased in recent years, particularly in the industrialized world. Allergic disease begins to manifest in the first years of life. The disorder usually manifests initially in the form of food allergy and atopic dermatitis, followed in later stages by respiratory allergy with rhinitis and/or asthma. This has led to the adoption of preventive measures in those children with a high risk of atopy, based on the following considerations: 1) A family history of allergic diseases (asthma, eczema, and/or allergic rhinitis); 2) A personal history of atopy such as atopic dermatitis, particularly when associated to food allergy; and 3) The existence of allergic sensitization, particularly to pneumoallergens, of early or late onset, but persistent during childhood. Prevention is established at three different levels: primary prevention, avoiding sensitization; secondary prevention, avoiding appearance of the disease; and tertiary prevention, avoiding the symptoms. The present study discusses current knowledge of prevention and its efficacy, with mention of the importance of breastfeeding and the use of pre- and probiotics for securing adequate prevention.     

Quoi de neuf en allergologie pédiatrique en 2004 ? Partie 3 : allergie cutanée,alimentaire, médicamenteuse et aux venins d'insectes (Une revue de la littérature internationale d'octobre 2003 à septembre 2004)

Severity and risk of persistence/relapse of atopic dermatitis are correlated with total IgE levels and food sensitization. Weaning to hypoallergenic formula improves SCORAD and gut barrier function in breastfed infants with persistent atopic dermatitis. Risk of anaphylaxis is high in children with cold-induced urticaria, and these children should be provided with an epinephrine autoinjector. Occult sensitizations are important risk factors for food allergy. The predictive values of serum egg-specific IgE levels are debated. The diagnostic value of atopy patch-tests with foods is confirmed in children with non-immediate food hypersensitivity reactions. Risk of persistence of food allergy is high in children with high specific IgE levels and/or with a low rate of decrease in food-specific IgE levels. Oral desensitization induces tolerance in children with persistent cow's milk allergy, except for children with very high levels of specific IgE. However, tolerance to anaphylactogenic food may be temporary, with the occurence of severe relapses after a few months. Ten per cent of children treated with penicillins are sensitized to these antibiotics. However, only a few of these children are at risk of developing allergy to penicillins. Non allergic hypersensitivity to non steroidal anti-inflammatory drugs is frequent in children. Sublingual immunotherapy may be efficient in children with latex hypersensitivity. A clinically important number of non-hyposensitized children do not outgrow hymenoptera venom allergy. In contrast, venom immunotherapy leads to a significantly lower risk of systemic reaction to stings. Thus, children with moderate to severe allergic reactions to hymenoptera stings should receive specific immunotherapy.     

Oral Allergy Syndrome

Oral allergy syndrome (OAS) is defined as the symptoms of IgE-mediated immediate allergy localized in the oral mucosa, and the characteristics depend on the lability of the antigen. Another term used for this syndrome is pollen-food allergy (PFS); the patient is sensitized with pollen via the airways and exhibits an allergic reaction to food antigen with a structural similarity to the pollen (class 2 food allergy). In addition to PFS, latex-fruit syndrome is also well-known as the disease exhibiting OAS. In treating the condition, it must be noted that most but not all symptoms of PFS are those of OAS. In many cases, antigens become edible by heating, but some are resistant to heating. Also, since the exacerbation of atopic dermatitis is occasionally observed after the intake of cooked antigens in asymptomatic individuals, careful inquiry of the history is important in designing the treatment. Immunotherapy against the cross-reacting pollen has also been attempted in PFS.     

Quoi de neuf en allergologie pédiatrique en 2005 ? Partie 4. Allergie cutanée,alimentaire, médicamenteuse et aux insectes (Une revue de la littérature internationale d'octobre 2004 à octobre 2005)

Allergological work-up and treatment of french children with atopic dermatitis have been the subject of a recent consensus. Food avoidance is useless for prevention of atopic dermatitis, and should be indicated in children with severe atopic dermatitis associated with food allergy only. Exposure, sensitization and allergy rates to nuts increase with age, and avoidance of nuts (even tolerated) is recommended in young children allergic to one or several nuts to prevent the risk of sensitization and allergy to an increasing number of nuts. Threshold values of skin prick-tests and specific IgE determinations with a 90-100% predictive value for food allergy are highly variable from one study to another one, and depend on numerous factors such as age of the children, the allergens used, etc. The diagnostic value of patch-tests and skin application food tests remains controversial. Treatment of food allergy is based on the eviction of the allergenic foods. However, probiotics and « desensitization » to foods may be efficacious in some patients. In children that have outgrown their food allergy, tolerance should be maintened by regular consumption of the foods. However, the parents should be informed that relapses requiring an emergency treatment may occur. Finallly, in children as in adults, repeated mosquito bites induce a desensitization, and most children outgrow their allergy between five to fourteen years.