Reactivity thresholds in children allergic to cow's milk and egg, but tolerant of baked milk and baked egg.

Background. The use of eliciting doses (EDs) for food allergens is necessary to inform individual dietary advice and food allergen risk-management. The Eliciting Dose 01 (ED01) for milk and egg, calculated from populations of allergic subjects undergoing diagnostic Oral Food Challenges (OFCs), are 0.2 mg total protein. The respective Eliciting Dose 05 (ED05) are 2.4 mg for milk and 2.3 mg for egg. As about 70% children allergic to such foods may tolerate them when baked, we sought to verify the EDs of that subpopulation of milk and egg-allergic children. Methods. We retrospectively assessed consecutive diagnostic OFC for fresh milk and egg between January 2018 and December 2020 in a population of baked food-tolerant children. Results. Among 288 children (median age 56 - IQR 36-92.5 months, 67.1% male) included, 87 (30.2%) returned positive OFC results, 38 with milk and 49 with egg. The most conservative ED01 were 0.3 mg total protein (IQR 0.03-2.9) for milk and 14.4 mg total protein (IQR 3.6-56.9) for egg. The respective ED05 were 4.2 (IQR 0.9-19.6) mg for milk and 87.7 (IQR 43-179) mg for egg. Such thresholds are respectively 1.5 (milk ED01), 1.75 (milk ED05), 72 (egg ED01), and 38.35 (egg ED05) times higher than the currently used thresholds. Conclusions The subpopulation of children allergic to milk and egg, but tolerant to baked proteins, displays higher reactivity thresholds than the general population of children allergic to milk and egg. Their risk stratification, in both individual and population terms, should consider this difference. In baked milk-tolerant children, milk causes reactions at lower doses than egg in our group of egg-tolerant children. This could be associated with the relative harmlessness of egg compared to milk in the determinism of fatal anaphylactic reactions in children

The clinical cross-reactivity and immunological cross-antigenicity of wheat and barley

Background: Some patients with a wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with a wheat allergy is due to cross-antigenicity between wheat and barley. In our study, we aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. Methods: We compared the results of barley oral food challenges (OFCs) before oral immunotherapy (OIT) for wheat with those after OIT in nine patients with a wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. Results: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. Conclusion: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat was one of the promising options for barley allergy.

Chronic Milk-Dependent Food Protein-Induced Enterocolitis Syndrome in Children from West Pomerania Region

Characteristics of chronic milk-dependent food protein-induced enterocolitis syndrome (FPIES) in children from the region of Western Pomerania were studied. Prospectively, 55 children were diagnosed at a median of 2.2 months. The open food challenges (OFC), morphologies, milk-specific IgE (sIgE) (FEIA method, CAP system), and skin prick tests (SPTs) were examined. Vomiting and diarrhea escalated gradually but quickly led to growth retardation. Of the infants, 49% had BMI < 10 c, 20% BMI < 3 c; 25% had anemia, and 15% had hypoalbuminemia. During the OFCs we observed acute symptoms that appeared after 2–3 h: vomiting diarrhea and pallor. A total of 42% children required intravenous hydration. Casein hydrolysates or amino acids formulae (20%) were used in treatment. In 25% of children, SPT and milk sIgE were found, in 18%—other food SPTs, and in 14% allergy to other foods. A transition to IgE-dependent milk allergy was seen in 3 children. In the twelfth month of life, 62% of children had tolerance to milk, and in the twenty-fifth month—87%. Conclusions. Chronic milk-dependent FPIES resolves in most children. By the age of 2 children are at risk of multiple food sensitization, and those who have milk sIgE are at risk to transition to IgE-mediated milk allergy. Every OFC needs to be supervised due to possible severe reactions.

IgE sensitisation predicts threshold but not anaphylaxis during oral food challenges to cow's milk

Predicting reaction threshold and severity are important to improve the management of food allergy, however the determinants of, and relationship between, these parameters are significant knowledge gaps. Identifying robust predictors could enable the reliable risk-stratification of food-allergic individuals. In this series of young people with CM-allergy undergoing DBPCFC – the largest reported in the literature – we did identify any baseline marker which predicted the occurrence of anaphylaxis at challenge, consistent with existing data. There is one report of IgE-sensitisation being predictive of severity in CM-allergy, however the authors included non-reactive patients in their analysis which significantly skewed the analyses, resulting in misleading conclusions. IgE-sensitisation in our cohort, particularly to casein, was predictive of LOAEL. Including an assessment of casein IgE may therefore be of clinical utility when evaluating patients with CM-allergy in the clinical setting.

Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects

Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.