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.     

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.     

Food allergy in gastroenterologic diseases： Review of literature

INTRODUCTION Food allergy is recognized as a common worldwide prob- lem, and, like other atopic disorders, its incidence seems to increase. Moreover, food-related allergic disorders are the leading cause of anaphylactic reactions treated in the emer- genc…     

Allergie à la farine de blé chez l’adulte

The clinical manifestations of allergy to wheat flour are similar to those of allergies to other foods. In adults, food-dependent exercise-induced anaphylaxis, chronic urticaria, and gastrointestinal food allergies (that is, irritable bowel syndrome, eosinophilic colitis, ulcerative colitis) are the most frequently described clinical manifestations of allergy to wheat. Wheat isolates, used as binders and emulsifiers in the food industry, are neo-allergens resulting from chemically induced desamidation of wheat gluten (heating at high temperature in an acidic medium). Wheat isolate allergens can induce severe systemic reactions (e.g., urticaria) and anaphylactic shock. Diagnosis consists of three steps: a suspicion based on the patient's history, identification of the allergen by skin testing and by laboratory tests, and confirmation by oral challenge or by an avoidance regime.     

Gastrointestinal food allergy: new insights into pathophysiology and clinical perspectives

Adverse reactions to food that result in gastrointestinal symptoms are common in the general population; while only a minority of such individuals will have symptoms due to immunologic reactions to foods, gastrointestinal food allergies do exist in both children and adults. These immune reactions are mediated by immunoglobulin E-dependent and -independent mechanisms involving mast cells, eosinophils, and other immune cells, but the complexity of the underlying mechanisms of pathogenesis have yet to be fully defined. Knowledge of the spectrum of adverse reactions to foods that affect the digestive system, including gastrointestinal food allergy, is essential to correctly diagnose and manage the subset of patients with immunologically mediated adverse reactions to foods. Potentially fatal reactions to food necessitate careful instruction and monitoring on the part of health care workers involved in the care of individuals at risk of anaphylaxis. New methods of diagnosis and novel strategies for treatment, including immunologic modulation and the development of hypoallergenic foods, are exciting developments in the field 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.     

Prevalence of food allergy in 137 latex-allergic patients.

There have been reports of increased prevalence of certain food allergies in patients with Type I latex allergy (LA). A detailed food allergy history was obtained from 137 patients with LA. Latex allergy was defined by positive history of IgE mediated reactions to contact with latex and positive skin prick test to latex and/or positive in vitro test (AlaSTAT and/or Pharmacia CAP). Food allergy was diagnosed by a convincing history of possible IgE mediated symptoms occurring within 60 minutes of ingestion. We identified 49 potential allergic reactions to foods in 29 (21.1%) patients. Foods responsible for these reactions include banana 9 (18.3%), avocado 8 (16.3%), shellfish 6 (12.2%), fish 4 (8.1%), kiwi 6 (12.2%), tomato 3 (6.1%), watermelon, peach, carrot 2 (4.1%) each, and apple, chestnut, cherry, coconut, apricot, strawberry, loquat, one (2.0%) each. Reactions to foods included local mouth irritation, angioedema, urticaria, asthma, nausea, vomiting, diarrhea, rhinitis, or anaphylaxis. Our study confirms the earlier reports of increased prevalence of food allergies in patients with LA. We also report increased prevalence of shellfish and fish allergy not previously reported. The nature of cross reacting epitopes or independent sensitization between latex and these foods is not clear.     

The diagnosis and management of egg allergy

Egg allergy is a common food hypersensitivity in children. Atopic dermatitis represents the main clinical manifestation in infancy. On first exposure, many of these infants present with urticaria, angioedema, or anaphylaxis. The role of egg allergy in gastrointestinal conditions is less well understood. The “gold standard” for the diagnosis of egg allergy is the double-blind, placebo-controlled food challenge. Diagnostic cut-off levels have been defined for food-specific serum immunoglobulin E antibody level and skin prick test wheal diameter that predict an adverse challenge outcome. This has significantly reduced the need for formal food challenges. Atopy patch testing, in conjunction with immunoglobulin E-based tests, may further improve the accuracy of predicting a positive challenge. The treatment of egg allergy consists of dietary elimination, or a maternal elimination diet in breast-fed infants. Approximately two thirds of infants with egg allergy will become tolerant by 7 years of age.     

Food allergy and food intolerance: diagnosis and treatment

Food allergy is a matter of concern because it affects about 0.5-3.8% of the paediatric population and 0.1-1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.     

Study of food allergy in the Spanish population

BackgroundThe aim of the study was to investigate the prevalence of food allergy in patients referred to our Allergy Unit and to evaluate the diagnostic methods used.MethodsWe selected 674 patients referred to the Allergy Unit of our hospital from May 2002 to October 2004. The prevalence of symptoms was determined by a standardized questionnaire, prick-prick test, and serum specific IgE. In a second phase, double- blind oral challenge tests were administered.ResultsFood allergy was found in 106 patients (15.7%): 71 adults (67 %) and 35 children (33 %). The prevalence of food allergen sensitization was 14 % in adults and 20.8 % in children. A total of 89.6 % of the patients experienced symptoms immediately. Only 29.2% the patients of sought medical attention and adrenaline was administered to five (16.1 %). The foods most frequently involved in allergic reactions were fruits (56.6%) and tree nuts (22.6%).The most common symptoms were oral allergy syndrome (46.2 %), urticaria (32.1 %), and anaphylaxis (14.2 %).Combining the results of the questionnaire with those of prick-prick tests in patients whose allergy was confirmed by double-blind, placebo-controlled food challenge (9.1 %) showed a sensitivity of 95.5 %, a negative predictive value of 96 %, a specificity of 75 % and a positive predictive value of 73%.Conclusions1. The prevalence of food allergy in our sample was 9.1 %. 2. The foods most frequently involved in allergic reactions were fruits and tree nuts. 3. The most common symptoms were oral allergy syndrome, urticaria, and anaphylaxis. 4. Combining our questionnaire with in vivo tests allowed us to diagnose 75-96% of patients with no food allergy and 95 % of food allergy patients.     

A case of milk allergy that presented anaphylaxis after cutaneous contact with allergen

Milk allergy in a 1-year and 8-month-old boy is reported. At 1 year and 1 month of age, the patient presented with anaphylaxis, including erythema, which was initially localized to the contact site of the anterior chest, and wheezing accompanied by dyspnea, 5 min after contact with milk allergen through his atopic skin. These symptoms continued for 50 min. Seventy minutes after the disappearance of the initial erythema, the patient developed subsequent erythematous lesions distributed throughout the neck and head area that persisted for as long as 24 h. On another occasion, he also exhibited a pale face and generalized erythema immediately after an accidental oral ingestion of milk at the age of 1 year and 8 months. He had been unsettled for several hours when an intravenous steroid was administered. His serum IgE was 590 IU/mL and the radioallergosorbent test (RAST) scores against milk, α-lactoalbumin, β-lactoglobulin, casein and cheese were 5, 2, 3, 5 and 5, respectively. This is a rare case of a patient with milk allergy who fell into anaphylaxis following both cutaneous contact with and oral ingestion of the offending milk protein. Care should be taken with patients with food allergies because cutaneous contact with the offending food may cause adverse reactions, including anaphylaxis.     

Exercise-induced anaphylaxis syndrome

In the last two decades a growing incidence of a peculiar form of anaphylaxis that only occurs while carrying out physical exercise has been observed. Within the exercise-induced anaphylaxis syndrome two well differentiated clinical forms are included: systemic cholinergic urticaria and exercise-induced anaphylaxis in the strict sense which can be shown by a classic form or a variant form, more uncommon and with manifestations similar to cholinergic urticaria. Postprandial or food-dependent exercise-induced anaphylaxis is a frequently identified subtype of these last cases. It can be due to an asymptomatic food allergy manifested through physical effort, although in many occasions it is not possible to find a responsible allergen. The diagnosis is settled on the clinical history and specific tests with food allergens. It can be necessary to perform an exercise challenge test with and without previous ingestion. The treatment is preventive and it is based on avoiding the food or the food allergen some hours before the exercise. When it does not depend on foods it is used a prophylactic pharmacotherapy with antihistamines, cromones or sodium bicarbonate. The patient should be well educated on the use of epinephrine in the event of new reactions.     

Latex-fruit syndrome

During the last decade, latex IgE-mediated allergy has been recognized as a very important medical problem. At the same time, many studies have dealt with allergic cross-reactions between aeroallergens and foods. In this context, there is clear evidence now on the existence of significant clinical association between latex and fruit allergies. Therefore, a latex-fruit syndrome has been postulated.Several studies have demonstrated that from 20% to 60% of latex-allergic patients show IgE-mediated reactions to a wide variety of foods, mainly fruits. Although implicated foods vary among the studies, banana, avocado, chestnut and kiwi are the most frequently involved. Clinical manifestations of these reactions may vary from oral allergy syndrome to severe anaphylactic reactions, which are not uncommon, thus remarking the clinical relevance of this syndrome.The diagnosis of food hypersensitivities associated to latex allergy is based on the clinical history of immediate adverse reactions, suggestive of an IgE-mediated sensitivity. Prick by prick test with the fresh foods implicated in the reactions shows an 80% concordance with the clinical diagnosis, and therefore it seems to be the best diagnostic test available nowadays in order to confirm the suspicion of latex-fruit allergy. Once the diagnosis is achieved, a diet free of the offending fruits is mandatory.Recently, some of the common allergens responsible for the cross-reactions among latex and the fruits most commonly implicated in the syndrome have been identified. Class I chitinases, with an N-terminal hevein like domain, which cross-react with the major latex allergen hevein, seem to be the panallergens responsible for the latex-fruit syndrome.     

Les allergies alimentaires

The incidence of food allergy appears to be on the increase in industrialized societies. The reasons suggested are consumption of new products and the evolution of food technology. The public perceives food allergies differently from doctors: adverse reactions to foods are misclassified as food allergies although they are in most of the cases non-allergic food intolerance or food aversion. Indeed, in controlled studies, a low prevalence of food allergy although they are in most of the cases non-allergy has been found (1–2% in adults, 2–8% in children). Despite a number of advances in the field of diagnosis and therapy, the standard methods of diagnosis and therapy for food allergies remain the same: double-blind placebo-controlled food challenge and avoidance. Reports on the effects of food processing indicate that certain processes for certain foods can either eliminate, reduce, or not change the allergenic potential. As more food allergen identification and information on the protein structures responsible becomes available, perhaps better ways to use processing methods to reduce or remove allergenicity may become apparent and feasible.     

"Atopy patch tests" in the diagnosis of delayed food hypersensitivity

The prevalence of atopic diseases is increasing worldwide. Food allergies are the earliest manifestation of atopy. Atopic eczema affects about 18% of infants in the first 2 years of life and the main cause is allergy to multiple foods. A strong association has been shown between atopic eczema and IgE mediated allergy to milk, egg or peanut, but more than two-thirds of patients intolerant to food proteins have no evidence of IgE sensitization to the relevant food protein. Recently, patch testing with proteins has been found to be helpful in diagnosing food allergy in cases where skin prick tests and estimation of specific antibodies have failed. The methodology of atopy patch test (APT) is unstandardized, and contradictory results have been reported. In contrast to the more standardized APT methodology with aeroallergens, the sensitivities and specificities of food allergens can easily be estimated with food challenge tests. With multiallergic children adding of APTs to the skin prick tests and specific antibody estimation tests give more information for planning a wide enough elimination diet to get the skin and gastrointestinal tract symptomless in order to perform the challenge test which remains the only reliable test for food allergy. Standardization of the APT materials and reading procedure will add to the reliability of this new test method.     

Elimination diet in the treatment of selected patients with hypersensitivity vasculitis.

We have evaluated the effects of an elimination diet in 5 patients with hypersensitivity vasculitis and a personal or family history of allergy. The presence of autoimmune disorders, infections and neoplastic diseases was excluded on the basis of physical examination, clinical history and laboratory data. Three patients had elevated serum immune complexes and evidence of complement consumption before the oligoantigenic diet. In one patient food allergy was diagnosed on the basis of a positive and concordant challenge test, skin prick test and RAST. The study consisted of a 3 week elimination diet, followed by open and double blind challenge tests with specific foods and additives. Four patients achieved a complete remission and one patient experienced great improvement on the elimination diet. In three cases the vasculitis relapsed following the introduction of food additives; in one case with the addition of potatoes and green vegetables (i.e., beans and green peas) and in the last case with the addition of eggs to the diet. The offending foods and additives were subsequently eliminated from the usual diet and no relapses were observed in 2 years of follow-up. These results show that in selected patients with a history of allergy, hypersensitivity vasculitis can be triggered and sustained by food antigens or additives.     

Oral Disodium Cromoglycate Treatment on Irritable Bowel Syndrome: An Open Study on 101 Subjects with Diarrheic Type

Several studies on the usefulness of oral disodium cromoglycate (DSCG) in the treatment of systemic adverse reaction to foods have been performed, with less attention to gastroenterological symptoms. In the present study, we selected 101 patients with diarrheic-type irritable bowel syndrome which improved after an elimination diet and worsened after a challenge with specific food(s). All patients were then tested for 48 commercial alimentary antigens by skin prick test (SPT) and underwent 8 wk of oral DSCG (500 mg three times a day), and the results were evaluated by means of a semiquantitative subjective and objective score. We observed an improvement of the symptoms in 67% of the 74 SPT-positive patients, whereas only 41% of the 27 SPT-negative patients showed a positive response to DSCG (p less than 0.05). These data confirm the protective role of DSCG in food-dependent diarrheic-type irritable bowel syndrome with food allergy features.     

Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge

Food allergy is becoming an increasingly common diagnosis. Because of this increase in prevalence, it is imperative that physicians evaluating patients with possible adverse reactions to foods understand the currently available assays and how they should best be used to accurately diagnose the disease. Simple tests such as skin prick testing (SPT) and serum food-specific IgE testing are the most commonly used diagnostic tests to evaluate for IgE-mediated food reactions. However, these tests, which measure sensitization and not clinical allergy, are not without pitfalls, and their utility must be appreciated to avoid over- and underdiagnosis. Although the physician-supervised oral food challenge remains the gold standard for food allergy diagnosis, a careful medical history paired with SPT and serum food-specific IgE testing often can provide a reliable diagnosis. In this review, we examine the usefulness and pitfalls of SPT and serum food-specific IgE levels, as well as examine atopy patch testing and other emerging tests, such as component-resolved diagnostics and the basophil activation test. Finally, we describe the use of the double-blind, placebo-controlled oral food challenge as the current gold standard for food allergy diagnosis.     

Chronic allergic-like dermatopathies in nickel-sensitive patients. Results of dietary restrictions and challenge with nickel salts.

Nickel frequently contaminates foods. In sensitized patients, dietary nickel can cause a relapse of contact eczema and also widespread chronic dermatopathies quite similar to those triggered by authentic food allergy (IgE-mediated), from atopic dermatitis to chronic urticaria with angioedema. The present study was intended to evaluate the the results of an elimination diet and of the oral challenge test with nickel salts in a population of adults suffering from chronic urticaria or angioedema, pruritus or atopic dermatitis, and concomitant contract sensitization to nickel salts. The study involved a population of adult patients (112 subjects, 106 women and 6 men, aged from 16 to 58, mean age 29 +/- 10) with widespread allergic-like dermatopathies and contact sensitization to nickel salts (positive patch test). All of these subjects were prescribed a low nickel diet for four weeks. The patients who recovered or whose clinical manifestations greatly improved underwent an oral double-blind, placebo-controlled challenge: they were administered two successive, noncumulative doses of 10 and 20 mg nickel sulphate hexahydrate, respectively equal to 2.23 and 4.47 mg of elemental nickel. A search for specific IgE and the check on skin reactivity by skin-prick test against nickel were carried out in the patients who had shown particularly severe reactions after the oral challenge. A low nickel diet was effective in controlling the symptoms in 44 patients (39.28%, among whom there was one man). The oral double-blind, placebo-controlled challenge test was positive in all the patients who had favourably responded to the elimination diet, except one. In the patients with anaphylactoid reactions on the oral challenge, skin-prick tests were negative and no serum-specific IgE antibodies against nickel were found. Such findings appear to demonstrate that, in some patients with concomitant contact allergy, intolerance to ingested nickel salts might be the real cause of the onset and perpetuation of widespread, chronic, allergic-type dermatopathies.