not-yet-known not-yet-known not-yet-known unknown Background: The innate immune system is activated at the onset of food protein-induced enterocolitis syndrome (FPIES) symptoms. However, the precise mechanism through which this immune response is initiated remains unclear. Objective: We aimed to investigate the proteomic profile of FPIES during symptom development through in-depth serum and saliva proteomic analyses. Methods: We enrolled 17 patients with a previous diagnosis of egg yolk FPIES who underwent an oral food challenge test (OFC) with 5 g of heated egg yolk. Six patients showed positive OFC results, whereas 11 showed negative OFC results. Serum and saliva samples were collected before OFC and 1 and 2 h after ingestion. Serum was also collected at symptom onset. We analyzed serum and saliva peptides using data-independent acquisition-mass spectrometry and compared levels to identify protein groups and pathways important in FPIES symptom development. Results: We detected 4,138 and 7,202 proteins in the serum and saliva, respectively. The OFC-positive group exhibited 609 serum proteins with more than a two-fold change in expression 2 h after OFC, including proteasome subunits and neddylation-related proteins. We identified 304 proteins associated with symptom onset, including those related to the degradation response and neutrophil extracellular trap formation. Proteins related to neutrophil activation increased both in the serum and saliva, regardless of the onset of symptoms. Conclusion: Our findings suggest that changes in protein levels, including proteasome and neddylation-related proteins, may be involved in FPIES pathogenesis and warrant further investigation to address the growing clinical burden imposed by gastrointestinal allergies.

Background: The primary treatment for anaphylaxis is intramuscular injection of adrenaline, but sometimes the response to treatment is inadequate and continuous intravenous administration of adrenaline is required. However, there is a lack of knowledge on the frequency and optimal method of administration. We aimed to report cases in which continuous adrenaline infusion was required during oral food challenges (OFCs) at our hospital. Method: We retrospectively reviewed the medical records of the last 6 years for cases of continuous Adrenaline administration in OFC. Result: Of 8531 patients, 214 patients received intramuscular adrenaline injection, and 7 patients required continuous administration. The reason for initiation of continuous administration was cardiovascular symptoms in all patients, one of which was associated with severe upper airway obstruction. All patients received intravenous fluid bolus, and one needed endotracheal intubation. Continuous infusion was started at 0.02-0.04 µg/kg/min, and because of prolonged hypotension in two patients, the dose had to be increased. Thereafter, all patients improved, and continuous administration was discontinued at a median of 155 (IQR:145-190) minutes. All patients had no adverse events or biphasic reactions. Conclusion: Continuous adrenaline administration in OFC was successful at 0.04-0.06 µg/kg/min in treating severe anaphylaxis refractory to multiple intramuscular injections of adrenaline, and therapeutic response was achieved at a lower dose than previously recommended (0.1-1.0 µg/kg/min).

Background: An oral food challenge (OFC) is required for diagnosing food allergies; however, uncertain reactions can impair the determination of when to stop the test. We aimed to determine the associations between immediately occurring mild allergic skin signs/laryngeal symptoms and positive OFC results. Methods: We retrospectively included children (aged 6 months to 15 years) who underwent open OFC for hen’s egg (HE), cow’s milk (CM), or wheat at a single centre between May 2012 and March 2020. Participants with mild skin signs or laryngeal symptoms at OFC initiation were classified as “skin” or “laryngeal” cases, respectively. Using logistic regression, the risk of positive OFC results, in a skin or laryngeal case, was assessed using univariate and multivariate analyses. Age, sex, total target dose, and serum levels of total and food-specific immunoglobulin E were used as covariates in prediction models. Results: In total, 2954, 1126, and 850 tests for HE, CM, and wheat, respectively, were included and comprised 115 (4%) and 25 (0.9%), 92 (9%) and 24 (2%), and 7 (1.3%) and 0 (0%) skin and laryngeal cases, respectively. Children with reactions to both HE and CM had a higher risk of a positive OFC than controls (odds ratio [95% confidence interval]: 4.6 [3.3–6.4], 2.9 [2.0–4.1] and 6.5 [3.0–10.9], 4.9 [2.2–10.9], respectively). Areas under the curves of prediction models ranged from 0.61 to 0.71. Conclusions: Uncertain reactions immediately after test initiation could not robustly predict OFC results, indicating the OFC could be continued under careful observation.