Food protein-induced enterocolitis syndrome (FPIES) caused by fish and others is prevalent in the Mediterranean regions but is less frequently reported in Japan. This case report describes a 3-year-old Japanese girl who developed FPIES triggered by multiple seafoods, including swordfish, cod, and squid. The diagnosis was confirmed through oral food challenge tests (OFC), which led to repeated vomiting and an increase in thymus and activation-regulated chemokine (TARC) levels. This case highlights the importance of considering fish-induced FPIES in the differential diagnosis of recurrent vomiting in children and suggests the potential utility of TARC levels in diagnosing and monitoring FPIES.

The use of extensively heated (EH) milk and egg products, and dietary advancement therapies such as milk and egg ladders is increasingly common for the management of milk and egg allergies. Although the majority of patients with milk and egg allergies will outgrow their allergies, the ability to tolerate extensively hydrolyzed forms of these allergens is an early indicator of developing long-term tolerance. The denaturation of conformational epitopes during the heating process reduces the allergenicity of these proteins, which makes patients who are EH tolerant more likely to tolerate progressively more of these proteins.

Oral immunotherapy (OIT) is an office-based procedure that offers potential treatment of immunoglobulin E mediated food allergy. OIT has multiple benefits, e.g., the ability to desensitize the individual with food allergy, which shifts the eliciting dose threshold required in that individual to trigger an allergic reaction, and also potentially to decrease the severity of any resulting reactions. However, OIT is not a cure and has distinct risks, including the risk of allergic reactions (including anaphylaxis) from the therapy itself, the potential risk of developing eosinophilic esophagitis (or similar clinical symptoms without a formal biopsy), and logistical issues in coordinating when to give the daily dose, and there are still uncertain intermediate-to-long-term outcomes with regard to OIT. The decision to start OIT is complex and potentially nuanced. Shared decision-making is a process that allows the patient and family and the clinician to undergo a mutual discussion of the risks, benefits, alternatives, and other considerations with regard to a medical decision (such as starting OIT) whereby there is an exchange of information that allows the patient and family to formally clarify and express their values and preferences with regard to facets of the decision in this particular context. The goal is for the patient to be able to make a fully informed decision that is reflective of his or her goals, values, preferences, and desires. This article outlined some of the key considerations to discuss with parents and patients before enrolling in an OIT program with regard to the risks and benefits, to assist in engaging in shared decision-making and obtaining informed consent.

BACKGROUND: Allergy to peanuts and tree nuts is a common cause of food allergy in Spain, with lipid transfer proteins (LTP) being the most frequently recognized panallergen. LTP sensitization often leads to multiple food group sensitivities, resulting in overly restrictive diets that hinder patient\'s quality of life. This study aimed to assess the tolerance of peanuts and tree nuts (hazelnuts and walnuts) in children sensitized to LTP, potentially mitigating the need for such diets.
METHODS: This prospective study enrolled individuals diagnosed with allergy to peanuts, hazelnuts, or walnuts. Data were collected from medical records, including demographics and clinical history. Allergological assessment comprised skin prick tests using commercial extracts and the nuts in question, alongside measurements of total and specific IgE to nuts and their primary molecular components. Participants showing positive LTP sensitization without sensitization to seed storage proteins underwent open oral nut challenges.
RESULTS: A total of 75 individuals labeled as allergic to peanuts, 44 to hazelnuts, and 51 to walnuts were included. All of them underwent an open oral provocation test with the incriminated nut, showing a high tolerance rate. Peanut was tolerated by 98.6% of patients, 97.72% tolerated hazelnut, and 84.3% tolerated walnut.
CONCLUSIONS: The findings suggest that the majority of patients allergic to peanuts, hazelnuts, or walnuts, due to LTP sensitization and lacking IgE reactivity to seed storage proteins, can tolerate these nuts. This supports the need for personalized nut tolerance assessments to avoid unnecessary dietary restrictions.

(1) Peanut allergy is associated with high risk of anaphylaxis which could be prevented by oral immunotherapy. Patients eligible for immunotherapy are selected on the basis of a food challenge, although currently the assessment of antibodies against main peanut molecules (Ara h 1, 2, 3 and 6) is thought to be another option. (2) The current study assessed the relationship between the mentioned antibodies, challenge outcomes, skin tests and some other parameters in peanut-sensitized children. It involved 74 children, divided into two groups, based on their response to a food challenge. (3) Both groups differed in results of skin tests, levels of component-specific antibodies and peanut exposure history. The antibody levels were then used to calculate thresholds for prediction of challenge results or symptom severity. While the antibody-based challenge prediction revealed statistical significance, it failed in cases of severe symptoms. Furthermore, no significant correlation was observed between antibody levels, symptom-eliciting doses and the risk of severe anaphylaxis. Although in some patients it could result from interference with IgG4, the latter would not be a universal explanation of this phenomenon. (4) Despite some limitations, antibody-based screening may be an alternative to the food challenge, although its clinical relevance still requires further studies.

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BACKGROUND: The peanut basophil activation test (BAT) has demonstrated excellent diagnostic accuracy with heparinized blood, but its clinical utility is limited by the short stability of samples stored in this anticoagulant.
OBJECTIVE: Using EDTA anticoagulated blood, these investigations determined if Peanut BAT sample stability can be extended to 2 days, the minimum stability requirement for diagnostic tests currently offered through American reference laboratories.
METHODS: Peanut non-allergic control (NAC), peanut IgE sensitized (PS), and peanut allergic (PA) children aged 6 months through 17 years were recruited from members of Kaiser Permanente Southern California. EDTA anti-coagulated blood samples were collected from participants, shipped to a centralized laboratory, and stored at 4oC for peanut BAT testing 1 and 2 days later.
RESULTS: Peanut BAT results for 23 unblinded participants were used to establish sample rejection and interpretation criteria that were subsequently validated in a prospective double-blind study involving 112 additional children (39-NAC, 36-PS, 37-PA). Of 105 blinded blood samples tested on each study day, 88 (84%) day-1 and 90 (86%) day-2 peanut BAT results were considered interpretable, with diagnostic accuracies of 95.5% and 94.4%, respectively. Moreover, all interpretable PA results were considered positive (100% sensitivity).
CONCLUSIONS: Using EDTA anti-coagulated blood samples collected remotely, 1 and 2 days before testing, study results highlight the favorable diagnostic performance characteristics of the peanut BAT and provide further evidence that the test could be readily operationalized for clinical use by interested commercial reference laboratories.

BACKGROUND: To avoid complete elimination of hen eggs (HE) from diet, we introduced a very-low-dose (VLD) oral food challenge (OFC) in patients with severe HE allergy in 2019. Herein, we investigated the efficacy of VLD HE OFC for achieving the full dose OFC.
METHODS: Patients with an overt allergic reaction to LD (1/32 HE [≤100 mg]) or less, egg white (EW) protein within 6 months were included. In the VLD group, patients not achieving full-dose OFC (1/2 HE: 1600 mg EW protein) within 2 years were excluded. We retrospectively compared the rate of passing a full-dose OFC between patients who underwent a LD OFC before 2019 (LD group) and those who underwent a VLD OFC (1/100 HE: 32 mg EW protein) after 2019 (VLD group). The period for passing the full-dose OFC was evaluated using Kaplan-Meier survival analysis.
RESULTS: We enrolled 411 and 111 patients in the LD and VLD groups, respectively. The median age at OFC initiation was 2.2 [1.5-3.6] and 2.1 [1.4-3.2] years in the LD and VLD groups, respectively. EW- and ovomucoid-specific IgE levels were 38.3 (12.5-72.9) and 21.0 (8.3-46.2) kUA/L in the LD group and 49.8 [18.8-83.9] and 32.1 [15.6-67.8] kUA/L in the VLD group, respectively. Over 4 years, the LD and VLD groups passed the full-dose OFC at rates of 70 and 95%, respectively, with significant differences (log-rank test, P < 0.001).
CONCLUSIONS: VLD HE OFC may contribute to passing a full-dose OFC in patients with severe HE allergies.

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BACKGROUND: Oral food challenge (OFC) is the criterion standard for diagnosis of acute food protein-induced enterocolitis syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated.
OBJECTIVE: To assess clinical-hematological changes and predictors of severity of FPIES reactions at OFC.
METHODS: This was an observational multicenter prospective study. Children aged 0 to 18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centers in Spain and Italy. OFC outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed on the basis of published \"2017 FPIES Consensus\" criteria. Clinical characteristics were recorded, and full blood cell count was done at baseline, reaction onset, and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC.
RESULTS: A total of 81 children had positive OFC (mild in 11% [9 of 81], moderate in 61% [49 of 81], and severe in 28% [23 of 81]). Increase in neutrophils and reduction in eosinophils, basophils, and lymphocytes were observed (P < .05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed that a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not sex, age, culprit food, cumulative dose, and previous reaction severity) was associated with reduced odds of severe reaction compared with giving multiple doses in a single day.
CONCLUSIONS: Distinct hematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may be associated with a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.