Elicitors and phenotypes of adult patients with proven IgE-mediated food allergy and non-immune-mediated food hypersensitivity to food additives.

BACKGROUND: Food allergy is a growing health concern with a prevalence of 2%-3% in the adult population in Europe. Non-immune-mediated food hypersensitivities, which include reactions after ingestion of food additives, affect 1% of adults and may resemble IgE-induced allergic reactions without identifiable immunologic sensitization. A double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for the diagnosis of any food hypersensitivity. OBJECTIVE: We analysed a large group of adult patients with suspected food hypersensitivity, who had undergone DBPCFC, to better understand IgE-mediated food allergy and non-immune-dependent food hypersensitivity to food additives in adults regarding elicitors, symptoms and positivity rates of oral challenges. METHODS: Data from 541 patients with suspected food hypersensitivity were analysed, who underwent an oral food challenge between 2010 and 2019. RESULTS: IgE-dependent food allergy was confirmed in 114 of 329 adult patients (34.6%). The confirmation rate was lower in the group of patients with suspected non-immune-mediated reactions to food additives (65 of 286, 22.7%). Urticaria and angioedema appeared more frequently in patients with IgE-mediated food allergies. By contrast, flush and diarrhoea were the most frequent symptoms after a challenge in the group with the non-immune-mediated reactions to food additives. Wheat and celery were the most frequently identified food allergens in adults, whereas colourings and preservatives were the most frequent elicitors of non-immune-mediated food hypersensitivity. CONCLUSION: The importance of oral food challenges for the diagnosis of food hypersensitivity is confirmed. IgE-dependent food allergy is more frequently proven, reaching a positivity rate of one-third and only about 20% for non-immune-mediated hypersensitivity. Future studies should elaborate on the mechanisms of non-immune-mediated food hypersensitivity and the clinical impact of cofactors in this setting.

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper.

BACKGROUND: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. METHODS: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. RESULTS: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. CONCLUSION: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.

[Loss of tolerance : Anaphylaxis after milk protein shake consumption in an adult sportsman]. / "Loss of tolerance" : Anaphylaxie nach Milcheiweißshake bei einem erwachsenen Sportler.

We describe the case of a man who developed an acute allergic reaction for the first time in his life directly after drinking a protein shake after a workout session. Allergy diagnostics, including skin prick testing and the determination of specific IgE antibodies revealed sensitizations to cow's milk and hen's egg. Due to the association between the onset of symptoms after ingestion of a milk protein shake, a type-1-allergic reaction to milk protein was suggested. The patient denied a provocation test, although this could have been an opportunity to elucidate the role of physical exercise in this case. We suspect in the present case a loss of tolerance of early childhood sensitization due to repetitive high protein exposure in the context of physical activity. The patient was provided information regarding dietary and emergency management.

[Management of severe nut allergy in adults]. / Management einer schweren Nussallergie im Erwachsenenalter.

We present a case of walnut allergy in a 24-year-old man. The allergy work up revealed sensitization to walnut including a positive skin prick test and a high value of walnut-specific IgEs. The patient showed an anaphylactic reaction during the double blind placebo-controlled food challenge, to a cumulative dose of 3.723 g of walnut protein. The oral food challenge resulted in counseling regarding strict walnut avoidance and optimization of the emergency management. At follow-up the patient reported that having adhered to the recommended dietary measures resulted in no further allergic reactions.

[Food-induced anaphylaxis - data from the anaphylaxis registry]. / Anaphylaktische Reaktionen auf Lebensmittel - Daten aus dem Anaphylaxie-Register.

Anaphylactic reactions due to food occur in the context of food allergy and, together with venom and drugs, are the most frequent elicitors of severe allergic reactions. In small children the most frequent elicitors of severe allergic reactions according to data from the anaphylaxis registry are hen's egg and milk, whereas in school children peanut and hazelnut are frequent elicitors of allergic reactions. Other frequent elicitors of anaphylactic reactions in childhood are wheat and soy. In adults the most frequent elicitors of severe allergic reactions due to food, based on data from the anaphylaxis registry, are wheat, soy, celery, shellfish and hazelnut. Rare elicitors of food-induced anaphylaxis in German-speaking countries are mustard and cabbage. However, the panel of rare elicitors of food-induced anaphylaxis show regional differences. As of March 2015, 17 cases of fatal anaphylaxis were registered and among these seven were food-induced. Co-factors can either trigger the elicitation of a severe allergic reaction or affect its severity. Among such co-factors are physical activity, the intake of certain drugs, and psychological stress. The data on the role of cofactors is sparse. The management of food-induced anaphylaxis includes acute management according to current guidelines, but also long-term management, which should include educational measures regarding treatment but also information about the food allergen in daily life.

Elicitors and co-factors in food-induced anaphylaxis in adults.

Food-induced anaphylaxis (FIA) in adults is often insufficiently diagnosed. One reason is related to the presence of co-factors like exercise, alcohol, additives and non-steroidal anti-inflammatory drugs. The objective of this analysis was to retrospectively investigate the role of co-factors in patients with FIA. 93 adult patients with suspected FIA underwent double-blind, placebo-controlled food challenges with suspected allergens and co-factors.The elicitors of anaphylaxis were identified in 44/93 patients. 27 patients reacted to food allergens upon challenge, 15 patients reacted only when a co-factor was co-exposed with the allergen. The most common identified allergens were celery (n = 7), soy, wheat (n = 4 each) and lupine (n = 3). Among the co-factors food additives (n = 8) and physical exercise (n = 6) were most frequent. In 10 patients more than one co-factor and/or more than one food allergen was necessary to elicit a positive reaction.The implementation of co-factors into the challenge protocol increases the identification rate of elicitors in adult food anaphylactic patients.