Faculty Bibliography

Background: While several scoring systems for the severity of anaphylactic reactions have been developed, there is a lack of consensus on definition and categorisation of severity of food allergy disease as a whole. Aim: To develop an international consensus on the severity of food allergy (DEfinition of Food Allergy Severity, DEFASE) scoring system, to be used globally. Methods: Phase 1: We conducted a mixed-method systematic review (SR) of 11 databases for published and unpublished literature on severity of food allergy management and set up a panel of international experts. Phase 2: Based on our findings in Phase 1, we drafted statements for a two-round modified electronic Delphi (e-Delphi) survey. A purposefully selected multidisciplinary international expert panel on food allergy (n = 60) was identified and sent a structured questionnaire, including a set of statements on different domains of food allergy severity related to symptoms, health-related quality of life, and economic impact. Participants were asked to score their agreement on each statement on a 5-point Likert scale ranging from "strongly agree" to "strongly disagree". Median scores and percentage agreements were calculated. Consensus was defined a priori as being achieved if 70% or more of panel members rated a statement as "strongly agree" to "agree" after the second round. Based on feedback, 2 additional online voting rounds were conducted. Results: We received responses from 92% of Delphi panel members in round 1 and 85% in round 2. Consensus was achieved on the overall score and in all of the 5 specific key domains as essential components of the DEFASE score. Conclusions: The DEFASE score is the first comprehensive grading of food allergy severity that considers not only the severity of a single reaction, but the whole disease spectrum. An international consensus has been achieved regarding a scoring system for food allergy disease. It offers an evaluation grid, which may help to rate the severity of food allergy. Phase 3 will involve validating the scoring system in research settings, and implementing it in clinical practice.

BACKGROUND:Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Symptoms are distinct from IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with Th17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood. OBJECTIVE:To use an untargeted metabolomics approach to identify novel pathways associated with FPIES reactions. METHODS:Serum samples were obtained before, during, and after an oral food challenge (OFC) (10 FPIES and 10 asymptomatic subjects), and they were analyzed by untargeted metabolomics. Two-way ANOVA with false discovery rate (FDR) adjustment was used for analysis of metabolites. Stomach and duodenal biopsies from non-FPIES donors were stimulated with adenosine in vitro and serotonin measured by immunoassay. RESULTS:A total of 34 metabolites were increased during symptomatic FPIES OFCs compared to asymptomatic subjects, including inosine and urate of the purine signaling pathway. Expression of purine receptors P2RX7 and P2RY10 and the ectonucleotidase CD73 in peripheral blood was significantly reduced after OFC in FPIES patients. The serotonin metabolite 5-hydroxyindoleacetate was significantly elevated post-reaction. Adenosine stimulation of gastric and duodenal biopsies from non-FPIES donors induced a significant release of serotonin, suggesting a link between purinergic pathway activation and serotonin release. CONCLUSIONS:Activation of the purinergic pathway during FPIES reactions provides a possible mechanism connecting inflammation and vomiting symptoms by triggering serotonin release from gastric and duodenal mucosa. CLINICAL IMPLICATIONS/CONCLUSIONS:The link between gastrointestinal inflammation and FPIES symptoms via adenosine and serotonin suggests novel therapeutic approaches to FPIES by targeting purinergic receptors.

Wheat is a dietary staple in many cultures as well as a common food allergen. Although not as extensively studied as other forms of oral immunotherapy, the current literature suggests that wheat oral immunotherapy (WOIT) can result in successful desensitization. There has only been one multicenter, double-blind, randomized controlled trial of WOIT, along with several open-label nonrandomized trials. The trials were limited by several factors, including small sample sizes; demographic skew; and heterogeneity in dosing, duration, and outcomes. The majority of WOIT regimens results in desensitization, with literature that indicates that a longer duration and higher dosing may lead to more clinical success. WOIT has been associated with adverse events, including allergic reactions, but these events seem to decrease over time. Study on WOIT is underway, but evidence from trials suggests it can be successful and safe. Further studies will need to optimize dosing protocols to improve efficacy and safety.

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines. We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.
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