Caroline Nilsson

Background: Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals.Methods: Blood and saliva from children undergoing upper endoscopy were analyzed for biomarkers, including absolute eosinophil count (AEC), eosinophil‐derived neurotoxin (EDN), total and specific IgG₄‐antibodies (sIgG₄), specific IgE‐antibodies (sIgE) and 15‐hydroxyeicosatetraenoic acid (15(S)‐HETE). Some patients participated twice, forming a longitudinal cohort. The ability to use the biomarkers to predict the EoE diagnosis was evaluated.Results: Analysis from 105 children divided into active EoE, remission, and healthy, revealed elevated levels of serum biomarkers (AEC, EDN, 15(S)‐HETE, sIgG₄, and sIgE) in active EoE compared to healthy individuals. A combination of biomarkers (AEC, EDN, sIgE to egg white and wheat) and symptoms showed an AUC of 0.92 in distinguishing between the three groups. We further showed that optimal cutoff values for these biomarkers could discriminate between active EoE and healthy with a sensitivity of 88% and a specificity of 100% in distinguishing EoE (active and in remission) from healthy. Longitudinally, levels of EDN, sIgG₄ to Bos d 4, Bos d 5, Bos d 8, gliadin, and birch, and sIgE to milk decreased in patients progressing from active EoE to remission (p <.05).Conclusions: This study identified novel biomarkers associated with EoE and proposes a panel, together with symptoms, for effective discrimination between active EoE, EoE in remission, and healthy individuals. The findings may contribute to a less invasive diagnostic method and may be a potential surveillance tool for pediatric EoE patients.

Background: There is substantial interest in immunotherapy and biologicals in IgE‐mediated food allergy.Methods: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random‐effects meta‐analysis.Results: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.–21.4, high certainty); cow's milk (RR 5.7, 1.9–16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4–18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2.Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0–1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7–3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1–7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4–19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8–3.8, moderate certainty). Results were unclear for other allergies and administration routes.There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions.Conclusions: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals.

Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on the type of food and mechanism, and it is not always easy to disentangle different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is immunoglobulin E (IgE)–mediated food allergy (prevalence 5–10%). Symptoms vary from mild itching, stomach pain, and rash to severe anaphylaxis. The definition of IgE‐mediated food allergy is allergic symptoms combined with specific IgE‐antibodies, and therefore only IgE‐antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children, and fish and shellfish in adults. In young children, milk/egg allergy has a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non‐IgE‐mediated food allergy, for example, eosinophilic esophagitis, celiac disease, food protein‐induced enterocolitis syndrome, and hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibilities of treating food hypersensitivity, such as through oral immunotherapy. The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions.

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labelling 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 labelling 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^th 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 5mg 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.

Background: Tree nut allergy may cause anaphylaxis. There are limited population‐based studies on prevalence and early‐life risk factors.Methods: We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population‐based cohort study and assessed early‐life factors associated with the development of tree nut allergy.We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early‐life risk factors.Results: Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non‐mild symptoms). Sixty‐three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (OR_adj 8.50 95% CI 2.15–33.6), eczema (OR_adj 2.53 95% CI 1.21–5.32) and asthma (OR_adj 5.59 95% CI 2.35–13.3)) at pre‐school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated.Conclusions: In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.

An early detection and follow‐up of children at risk of developing allergic diseases is crucial to optimize treatment and increase well‐being. A clinical history is the most important tool when diagnosing allergic diseases; however, IgE‐antibody (IgE) testing can obtain additional information. We have previously evaluated Phadiatop Infant^® (Phinf), a test analyzing IgE to 11 common inhalant and food allergens, at 2 and 5 years of age, showing a sensitivity and specificity over 84 % for detecting IgE sensitizations during childhood.