Food Intolerances and Eosinophilic Esophagitis in Childhood

Food intolerance is an adverse reaction to a particular food or ingredient that may or may not be related to the immune system. A deficiency in digestive enzymes can also cause some types of food intolerances like lactose and gluten intolerance. Food intolerances may cause unpleasant symptoms, including nausea, bloating, abdominal pain, and diarrhea, which usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may delayed up to 48 h. There is also a strong genetic pattern to food intolerances. Intolerance reactions to food chemicals are mostly dose-related, but also some people are more sensitive than others. Diagnosis can include elimination and challenge testing. Food intolerance can be managed simply by avoiding the particular food from entering the diet. Babies or younger children with lactose intolerance can be given soy milk or hypoallergenic milk formula instead of cow’s milk. Adults may be able to tolerate small amounts of troublesome foods, so may need to experiment. Eosinophilic esophagitis (EE) is defined as isolated eosinophilic infiltration in patients with reflux-like symptoms and normal pH studies and whose symptoms are refractory to acid-inhibition therapy. Food allergy, abnormal immunologic response, and autoimmune mechanisms are suggested as possible etiological factors for EE. This article is intended to review the current literature and to present a practical approach for managing food intolerances and EE in childhood.     

HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods

The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including “in vivo” and “in vitro” allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H₂ breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance.     

Japanese Guideline for Food Allergy

Food allergy is defined as “a phenomenon in which adverse reactions (symptoms in skin, mucosal, digestive, respiratory systems, and anaphylactic reactions) are caused in living body through immunological mechanisms after intake of causative food.”Various symptoms of food allergy occur in many organs. Food allergy falls into four general clinical types; 1) neonatal and infantile gastrointestinal allergy, 2) infantile atopic dermatitis associated with food allergy, 3) immediate symptoms (urticaria, anaphylaxis, etc.), and 4) food-dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate-type food allergy).Therapy for food allergy includes treatments of and prophylactic measures against hypersensitivity like anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be conducted only if they are inevitable because they places a burden on patients. For this purpose, it is highly important that causative foods are accurately identified. Many means to determine the causative foods are available, including history taking, skin prick test, antigen specific IgE antibodies in blood, basophil histamine release test, elimination diet test, oral food challenge test, etc. Of these, the oral food 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.     

腹泻型肠易激综合征患者食物不耐受、症状指数及回盲部肥大细胞变化的相关性

目的:比较食物不耐受(food intolerance,FI)在腹泻型肠易激综合征患者(diarrhea-dominant irritable bowel syndrome,D-IBS)及健康人群中的存在情况,分析D-IBS患者食物不耐受严重程度、症状指数与回盲部肥大细胞数量变化之间的关系,以探讨食物不耐受在D-IBS发病中的意义及可能机制.方法:选取符合罗马Ⅲ诊断标准的D-IBS患者22例为病例组,无消化系症状的健康体检者21例为对照组,分别接受结肠镜检查.应用食物不耐受状况评价问卷对2组进行食物不耐受状况评分;用功能性肠病症状严重指数(functional bowel disorder severity index,FBDSI)和IBS病情尺度调查表(IBS symptomseverity scale,IBS-SSS)对病例组进行IBS症状严重程度评分.所有研究对象均接受结肠镜检查,在距回盲瓣4cm处取活检组织2块,采用甲苯胺蓝染色法计数黏膜肥大细胞数量,并与食物不耐受严重程度指数、IBS症状严重程度评分进行相关性分析.结果:D-IBS患者回盲部肠黏膜肥大细胞计数(4.68±0.55)个/高倍镜视野,健康对照组为(1.33±0.54)个/高倍镜视野,P<0.001,差异具有统计学意义;病例组食物不耐受存在情况明显高于对照组(P<0.05);食物不耐受严重程度与IBS症状严重程度指数间呈正相关(FBDSI:r=0.992,P<0.001;IBS-SSS:r=0.970,P<0.001);回盲部肥大细胞计数与I B S症状严重程度指数间呈正相关(FBDSI:r=0.957,P<0.001;IBS-SSS:r=0.985,P<0.001);食物不耐受严重程度与IBS患者回盲部肥大细胞计数间呈正相关(r=0.964,P<0.001),健康对照组中食物不耐受者回盲部肥大细胞计数明显高于无食物不耐受者(P<0.05).结论:D-IBS临床症状与肠道肥大细胞数量增多密切相关,食物抗原的刺激作用可能是D-IBS患者回盲部肥大细胞数目增多的原因之一;D-IBS患者食物不耐受存在情况普遍,食物不耐受可加重D-IBS患者肠道症状.     

Symptoms of food allergy

Adverse reactions to foods can be due to many causes, but only those involving an immunological mechanism can be defined as food allergic disease. An increasing number of gastrointestinal and other diseases are being shown to involve food intolerances. Immediate reactions with symptoms within hours of eating a particular food are most readily shown to be due to food allergy and are often associated with the presence of food-specific IgE as shown by skin prick tests and RASTs. When reactions are delayed for 24 to 48 hours or more, underlying food intolerance is harder to recognize and much less often shown to be due to allergy. At present, diagnosis and management depends on dietary manipulation, showing that symptoms improve on food avoidance and are reproduced by food challenge (preferably double-blind). Further understanding of the mechanisms involved in food allergy, in Crohn's disease and irritable bowel syndrome may allow the development of simple tests to identify the foods concerned and perhaps, in the case of allergic disease, cure by the induction of tolerance.     

Food allergy and the respiratory tract

Previous studies have confirmed that IgE-mediated, food allergy-induced respiratory tract symptoms occur, typically accompanied by cutaneous or gastrointestinal symptoms. The possibility that respiratory tract symptoms are food allergy induced should be considered in patients who have a current or past history of one or more of the following: atopic dermatitis, wheezing (or experiencing anaphylactic symptoms) after ingesting a particular food or foods, and confirmed food allergy. Moreover, the work-up of food allergy in asthma should be considered in patients in whom asthma is poorly controlled despite persistent use of appropriate asthma medications. A definitive diagnosis of food allergy should be based on clinical history, appropriate laboratory testing, and, when indicated, well-controlled oral food challenges. Treatment is based on establishing a safe elimination diet and an emergency plan for managing reactions caused by accidental ingestion.     

Gastrointestinal Food Allergy in Infants

Food allergies are classified into three types, “IgE-mediated,” “combined IgE- and cell-mediated” and “cell-mediated/non-IgE-mediated,” depending on the involvement of IgE in their pathogenesis. Patients who develop predominantly cutaneous and/or respiratory symptoms belong to the IgE-mediated food allergy type. On the other hand, patients with gastrointestinal food allergy (GI allergy) usually develop gastrointestinal symptoms several hours after ingestion of offending foods; they belong to the cell-mediated/non-IgE-mediated or combined IgE- and cell-mediated food allergy types. GI allergies are also classified into a number of different clinical entities: food protein-induced enterocolitis syndrome (FPIES), food protein-induced proctocolitis (FPIP), food protein-induced enteropathy (Enteropathy) and eosinophilic gastrointestinal disorders (EGID). In the case of IgE-mediated food allergy, the diagnostic approaches and pathogenic mechanisms are well characterized. In contrast, the diagnostic approaches and pathogenic mechanisms of GI allergy remain mostly unclear.In this review, we summarized each type of GI allergy in regard to its historical background and updated clinical features, offending foods, etiology, diagnosis, examinations, treatment and pathogenesis. There are still many problems, especially in regard to the diagnostic approaches for GI allergy, that are closely associated with the definition of each disease. In addition, there are a number of unresolved issues regarding the pathogenic mechanisms of GI allergy that need further study and elucidation. Therefore, we discussed some of the diagnostic and research issues for GI allergy that need further investigation.     

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.     

Gastrointestinal allergy in adults

The prevalence of food allergy reaches 3% in the adult population. Chronic gastrointestinal allergy is a rare entity: 4.2% of food allergies in adults, and represents 3.2% of all intestinal disorders. Non-specific symptoms are the rule but eosinophilic gastrointestinal disorders are the subject of much interest. Endoscopy and biopsies of the gastrointestinal tract help the differential diagnoses. Food allergy is suspected from the patient's history leading to skin tests and laboratory tests identifying a sensitization but allergy is only confirmed by standardized challenges or eviction diets over a sufficiently long period. New types of investigations coupling oral challenges to foods to gastroenterological techniques should be studied further.     

Gastrointestinal food hypersensitivity: Symptoms, diagnosis and provocation tests.

As many as 25% of the general population in Western countries believe that they suffer from adverse reactions to food. However, the actual prevalence of food allergy is much lower. Food-induced allergic reactions cause a variety of symptoms including cutaneous, gastrointestinal and respiratory tract. Food allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE-mediated (cellular) mechanisms. The clinical diagnosis is based on a careful history, laboratory findings (total and specific IgE), skin prick test, elimination diet and food challenges. New intestinal provocation tests have also been applied to pick up the allergic response of the duodenal mucosa by endosonography and external ultrasound. The management of food allergy continues to be a strict avoidance of the offending food item.     

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.     

Gastrointestinal food allergies: do they exist?

Gastrointestinal (GI) symptoms are often attributed to adverse reactions to foods (ARF), but it is not always clear whether such reactions are caused by food allergy. A reaction to food proteins that is mediated by immunologic events is referred to as food allergy or food hypersensitivity. One of the most common types of food allergy is the IgE-mediated immediate hypersensitivity reaction to foods, which can give rise to dermatologic and respiratory tract symptoms in addition to GI complaints. Other GI forms of food allergy include food protein-induced enterocolitis or gastroenteropathy, celiac disease, and some cases of eosinophilic gastroenteritis. Because most patients complaining of adverse reactions to food have non-immune mechanisms for their complaints, it is important to distinguish the various types of ARF, as their management may differ substantially. Recent advances in the field of food allergy provide opportunities to improve diagnostic methods and develop new modalities for management that will complement the current practice of allergen avoidance.     

Asthma and food allergy

PURPOSE OF REVIEW: Food allergy associated clinical and social burdens have increased substantially in prevalence in the past decade. Coexisting asthma is a significant problem as food reactions tend to be more severe when they involve the lung. Food allergy also increases asthma morbidity in adults and children. RECENT FINDINGS: Especially in early infancy, food allergy can be related to the development of future asthma. For diagnosis, cut-off values are very important for both specific IgE levels and skin-prick test when interpreting food allergy. For the treatment, oral immunotherapy is showing promise for refractory patients with IgE-mediated food allergies. SUMMARY: Food allergies can be classified as IgE-mediated or non-IgE-mediated. Besides foods, some additives and preservatives can also trigger asthma in certain people. Asthma may develop in about 5% of individuals who suffer from food allergy and current asthma may be triggered by foods among 6-8% of children and 2% of adults. Because of the difficulty of confirming diagnosis of food allergy, novel approaches are currently being investigated and new therapy modalities are being sought. For total asthma control and for better quality of life, steps should be taken to avoid foods in cases of food allergy.     

Hidden fish substance triggers allergy.

Food allergy (hypersensitivity) is a form of adverse food reaction caused by an immunological response to a particular food. IgE-mediated food allergy is responsible for most immediate-type food-induced hypersensitivity reactions. The prevalence of food allergy in the general population, not including oral allergy syndrome, is about 1-2%. While adults might tend to be allergic to fish, crustaceans, peanuts, and tree nuts, children, on the other hand, tend to be allergic to cow's milk, egg white, wheat, and soy. Food is the most common eliciting factor of anaphylaxis (45%), followed by drugs (29%), and insect stings (21%). Our study describes a 3 1/2-year-old boy who is allergic to fish consumed via ingestion and inhalation. This case is a good example of how easily people with food allergies can unintentionally consume foods to which they allergic, and is a clear demonstration of the dangers of such effects.     

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. There is conflicting evidence in the literature on the role for IgE mediated allergy in gastrointestinal reactions to staple foods. AIM: The aim was therefore to study the role of IgE mediated allergy in a group of patients with a history of gastrointestinal symptoms related to staple foods (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC, identified by screening of 96 consecutive patients referred to our allergy clinic for investigation of suspected gastrointestinal symptoms due to staple foods. METHODS: The screening included diaries as well as elimination diets and open and blinded food challenges. The frequency of atopy were compared between the double blind positive and double blind negative patients. RESULTS: The positive DBPCFC in the 15 patients included eight patients with milk intolerance, four with wheat flour, two with egg, and one with rye flour. There was no indications of an allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick test and radioallergosorbent test were negative for the relevant allergens. The frequency of atopy was four of 21 (19%) in the double blind negative group and three of 15 (20%) in the double blind positive group. CONCLUSION: In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods suggesting other mechanisms in adults than in children. Future studies may include measures of local events in the shock organs in relation to food intake, for instance utilising inflammatory markers in jejunal fluids.     

Role of alimentation in irritable bowel syndrome

BACKGROUND: Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. AIMS: During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. METHODS/RESULTS: Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. CONCLUSION: Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients.     

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.     

Extensively hydrolyzed formula (MA-mi) induced exacerbation of food protein-induced enterocolitis syndrome (FPIES) in a male infant.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated food allergy in which digestive symptoms such as severe vomiting and diarrhea are induced by cow's milk and/or soy protein in infants. Generally, a food-specific IgE is not detected, and FPIES may be caused by inadvertent exposure to allergenic foods. CASE SUMMARY: The patient in our case was a male infant in whom vomiting had been induced by ingestion of a cow's milk-based formula and bloody diarrhea had been caused by ingestion of breast milk during the neonatal period. Accidental ingestion of a new and extensively hydrolyzed casein/whey formula, MA-mi, caused watery diarrhea at 8 months of age, and FPIES was diagnosed based on these symptoms. In antigen-specific lymphocyte stimulation tests, New MA-1 was negative, but MA-mi and cow's milk antigens were positive. The only causative antigens were derived from cow's milk, and the symptoms were not induced by another extensively hydrolyzed casein formula, New MA-1. The patient grew and developed normally thereafter, and no symptoms were induced by solid food during the course of the condition. DISCUSSION: MA-mi is likely to be used increasingly for allergic infants, but it is not necessarily a substitute for other hydrolyzed milk formulae in all cases, and care should be taken regarding its use and possible misuse.     

Guidelines for diagnosis and management of pediatric food allergy in Japan.

In Japan, the prevalence of food allergy has been increasing and a variety of problems have emerged regarding what should be considered a food allergy. A treatment regimen consists of avoiding the offending food (elimination diet therapy) and receiving nourishment from alternative foods (substitutional diet therapy). There is a growing concern that confusion has resulted from the lack of a consensus on the procedures for diagnosing and treating food allergies. The Food Allergy Committee of the Japanese Society of Pediatric Allergy and Clinical Immunology established the "Guidelines for Diagnosis and Management of Pediatric Food Allergy." Definition, classification, pathophysiology, clinical disorders and management of food allergy are discussed and determined.     

Food intolerance and Crohn's disease.

It has been claimed that prolonged remissions of Crohn's disease can be achieved after enteral or parenteral nutrition, by identifying and excluding foods that exacerbate a patient's symptoms. The occurrence of food intolerances were assessed after induction of remission with elemental diet in 42 eligible patients to whom single foods were introduced over five days. Suspect foods were reinvestigated with open and if possible, double blind rechallenge. Fourteen patients (33%) dropped out of the study because of relapse of disease unrelated to food (n = 8) or because of difficulties in complying with the regimen (n = 6). Twenty (48%) of the patients identified food sensitivities whereas eight (19%) did not. Seventeen of the patients who identified food sensitivities had an open rechallenge with recurrence of symptoms in 10 (24% of total). Food sensitivity was confirmed in three patients on double blind challenge. There was no significant difference in the duration of remission between patients who did or did not identify food sensitivities. During the study three cases of intolerance to the formula diet, and one of severe salicylate sensitivity were encountered. In conclusion food sensitivities are evident after treatment of Crohn's disease with elemental diet but are variable, often do not persist, and are of insufficient importance to warrant putting all patients through elimination diets.