Background: Oral food challenges (OFCs) are still the reference standard for confirming food allergy, yet the influence of previous anaphylaxis on challenge outcomes remains uncertain. Patients with a history of anaphylaxis are often considered at higher risk, which may affect the clinical decision-making process. This study aimed to identify predictors of OFC failure stratified by a history of anaphylaxis, given that prior investigations have predominantly considered anaphylaxis as an overall risk factor, without delineating distinct risk factor profiles according to anaphylaxis history. Methods: We conducted a retrospective evaluation of standard-of-care pediatric OFCs to cow’s milk and hen’s egg white. Eligible children had suspected or confirmed IgE-mediated allergy to cow’s milk protein (CMP) or hen’s egg white protein (HEWP) and were stratified by the presence or absence of previous anaphylaxis to the challenged food. Clinical data were compared between groups. Open OFCs were conducted under inpatient supervision with full emergency support. Logistic regression models were used to assess the relationship between comorbidities, specific IgE (sIgE) concentrations and OFC outcomes. Receiver operating characteristic (ROC) analysis evaluated diagnostic accuracy of sIgE concentrations in predicting OFC outcomes. Results: The analysis included 192 pediatric patients undergoing OFCs: 106 to CMP and 86 to HEWP. Six challenges (3.1%) were inconclusive, giving 186 valid results. The overall OFC failure rate was 32.3%. Patients with a past history of anaphylaxis more frequently underwent cow’s milk challenges (p = 0.01). Atopic dermatitis was a more common comorbidity in those without prior anaphylaxis (p = 0.04), regardless of the trigger. In hen’s egg challenges, children with a history of anaphylaxis reacted to significantly lower cumulative doses (p = 0.03) than patients without. Atopic dermatitis was identified as a predictor of OFC failure in children without prior anaphylaxis (p = 0.02), and asthma as a borderline predictor in those with previous systemic reactions (p = 0.05). Specific IgE concentrations correlated with OFC outcomes across allergens, with casein-sIgE showing the highest discriminative performance (AUC = 0.81) in children without previous anaphylaxis. Conclusions: Atopic dermatitis and asthma were identified as potential risk factors influencing OFC outcomes, depending on the patient’s history of anaphylaxis. The predictive accuracy of sIgE was different in groups stratified by presence of prior anaphylaxis, and the relationship between sIgE concentration and clinical reactivity was not identical across the two subpopulations. Casein-sIgE showed the highest diagnostic accuracy in children without previous severe reactions to CMP. Presence of anaphylactic reactions in the past is an important consideration when selecting children for OFCs to CMP and HEWP, since it delineates distinct risk factors for challenge failure in these patient populations.

Background: Oral food challenges (OFCs) are still the reference standard for confirming food allergy, yet the influence of previous anaphylaxis on challenge outcomes remains uncertain. Patients with a history of anaphylaxis are often considered at higher risk, which may affect clinical decision-making process. In our study, we sought to identify predictors of OFC failure stratified by previous history of anaphylaxis. Methods: We conducted a retrospective evaluation of standard-of-care OFCs to cow’s milk and hen’s egg white performed between January 2014 and July 2025 at the Pediatric Allergy Center. Eligible participants had suspected or confirmed IgE-mediated allergy to cow’s milk protein (CMP) or hen’s egg white protein (HEWP), and were classified according to the presence or absence of previous anaphylaxis to the challenged food. Clinical data, including age, gender, allergic comorbidities, family history of atopy, and levels of specific IgE (sIgE) were obtained from medical records and compared between groups. Open OFCs were conducted according to PRACTALL guidelines (2012/2024) under inpatient supervision with full emergency support. Specific IgE levels were measured using the ImmunoCAP® assay (Phadia, Uppsala, Sweden). Logistic regression models were used to assess the relationship between comorbidities, sIgE concentrations and OFC outcomes. Receiver operating characteristic (ROC) analysis evaluated diagnostic accuracy of sIgE levels in predicting OFC outcomes. Results: The analysis included 192 pediatric patients (median age 4.75 years, 66.1% male) undergoing OFCs: 106 to CMP and 86 to HEWP. Six challenges (3.1%) were inconclusive, giving 186 valid results. The overall OFC failure rate was 32.3% (30.2% to CMP and 34.9% to HEWP). Patients with a past history of anaphylaxis more frequently underwent cow’s milk challenges (p = 0.01). Atopic dermatitis was a more common comorbidity in those without prior anaphylaxis (p = 0.04), regardless of the trigger. In hen’s egg challenges, children with a history of anaphylaxis reacted to significantly lower cumulative doses (p = 0.03) than patients without. Logistic regression analysis identified atopic dermatitis as a predictor of OFC failure in children without prior anaphylaxis (p = 0.02), and asthma as a borderline predictor in those with previous systemic reactions (p = 0.05). Specific IgE levels correlated with OFC outcomes across allergens, with casein-sIgE showing the highest discriminative performance (AUC = 0.81) in children without previous anaphylaxis. Conclusions: Atopic dermatitis and asthma were identified as potential risk factors influencing OFC outcomes, depending on the patient’s history of anaphylaxis. The predictive accuracy of sIgE was different in groups stratified by presence of prior anaphylaxis. Casein-sIgE showed the highest diagnostic accuracy in children without previous severe reactions to CMP. A prior history of anaphylaxis was associated with increased allergen sensitivity but did not predict a higher risk of severe reactions during supervised OFCs. Presence of anaphylactic reactions in the past is an important consideration when selecting children for OFCs to CMP and HEWP, since it delineates distinct risk factors for challenge failure in these patient populations.