Egg allergy is among the most common food allergies in early childhood, with prevalence estimates of 0.5%–2% across populations.1, 2 Existing care pathways typically involve strict avoidance with intermittent oral food challenges (OFC), or Dietary Advancement Therapies (DATs), such as home-based “egg ladders”.3, 4 Guidelines endorse egg ladders as a pragmatic option in selected patients, yet clinicians lack prognostic biomarkers to guide decision-making and counseling at diagnosis. Egg ladders for managing IgE-mediated egg allergies have become increasingly adopted as first-line management.5 The ladders involve the stepwise, home-based reintroduction of the allergen from baked forms at the bottom of the ladder to partially/lightly cooked and eventually raw forms.3, 4 Ladders additionally take advantage of combining the allergen in a wheat matrix when baked.6 The primary advantage of the ladders over conventional avoidance is reducing the length of time strictly avoiding all allergen-containing foods.7 Due to the ubiquitous nature of egg-containing products in the Western diet, this considerably decreases disease burden. Component-resolved diagnostics (CRD) are established in food allergy for diagnostic refinement and, in some settings, risk stratification.8, 9 In egg allergy, Gal d 1 (ovomucoid) and Gal d 2 (ovalbumin) specific IgE (SpIgE) have been associated with reactivity profiles in cohorts managed by avoidance with OFC.10 However, whether baseline component levels predict outcomes in ladder-based management remains uncertain. We investigated whether SpIgE to egg and egg components at diagnosis are associated with subsequent tolerance outcomes on an egg ladder. We conducted a single-centre, retrospective observational study of children aged ≤3 years with IgE-mediated egg allergy attending a tertiary pediatric service between 2021 and 2023. Inclusion required serum SpIgE to egg or egg white >0.35 KUA/L at diagnosis and active use of the Irish Food Allergy Network (IFAN) egg ladder. Exclusion criteria were age >3 years at test date, absence of ladder use or less than 6-month follow-up after IgE measurement. Past electronic health records, including medical and dietetic letters, were reviewed up to a single time point (March 2026) to assess demographics, allergic comorbidities, dietetic input, ladder duration, and date tolerance achieved or highest tolerance level achieved. As per local guidelines, patients have component testing at diagnosis and begin DAT at this stage with reviews every 6 months to 1 year. Institutional Board Review approval was received from the Clinical Research Ethics Committee of Cork Teaching Hospitals (CREC) on the 05/09/2023 and patient consent was deemed not necessary given the retrospective study design. The IFAN ladder was categorized as follows: Step 1 (well-cooked egg; up to and including pancake), Step 2 (partially cooked egg; up to and including omelette), Step 3 (almost raw/raw). The primary outcome was the association between baseline SpIgE (egg white) and egg components (ovomucoid, ovalbumin) and the time of tolerance to egg achieved. Secondary outcomes were associations between age at ladder start, gender, peanut/tree nut/other food allergies, and dietetic input with ladder outcomes. A descriptive statistical analysis was carried out for all collected variables. Normally distributed data were expressed as mean and standard deviation; non-normal data as median and interquartile range; and categorical variables were reported as percentages. To assess the time to egg tolerance, a survival analysis was used. To assess the association between IgE components and time to egg tolerance, univariate and multivariate Cox proportional hazard regressions were used. Data was analyzed using Jamovi statistical software. We analyzed 51 children with a median age at diagnosis of 1.4 years (IQR = 1.04) and median age of most recent follow-up or reaching tolerance to raw egg of 3.42 years (IQR = 1.54). Baseline demographics are in Table 1. Full raw egg tolerance was achieved in 28 (55%) cases, partial egg tolerance in 17 (33%) cases, and minimal tolerance in 6 (12%) of cases. A cumulative events curve with 95% confidence interval was generated to illustrate the overall time to egg tolerance in the cohort (Figure 1). There was an 6% chance of tolerance to raw egg by year 1 (CI: 0%–13%) and a 93% chance of tolerance by year 5 (CI: 57%–99%). Univariate Cox regression analyses were completed to assess for any significant association between SpIgE to Egg white, ovomucoid and ovoalbumin. These showed no significant increased or decreased likelihood of becoming tolerant related to these 3 components as shown in the below Table 2. Due to high standard deviation, the log result of components was also analyzed (Table 2). A multivariate analysis of egg white specific IgE with potential confounders (dietetic input, age of ladder initiation, and comorbid peanut allergy) also showed no significant increased risk with high Specific IgE to egg white (multivariate hazard ratio = 1 (0.97–1.02)). Our findings indicate that, in a real-world ladder-based management context, baseline egg component SpIgE does not adequately predict the pace or extent of tolerance progression. This contrasts with reports from avoidance/OFC-based cohorts where ovomucoid can indicate baked egg reactivity or persistence.10 Borderline results for ovomucoid and a non significant trend towards specific IgE to Egg White show promise and more focused, larger scale investigations into components use in DAT would be beneficial. Nevertheless, this study implies that biomarker performance is context-dependent and will not translate reliably from diagnostic to prognostic applications within DAT protocols. Clinically, these results caution against using component levels at diagnosis as gatekeepers for ladder eligibility or as prognostic tools for ladder trajectory. Instead, decisions should continue to centre on careful clinical history and safety planning. CRD should support diagnosis and specific risk discussions rather than dictating DAT candidacy or expected timelines. The observed relationship between time on the ladder and achieving tolerance supports current practice favoring early, structured reintroduction in suitable patients. Ladders may reduce the period of total avoidance, enable earlier inclusion of baked allergens, and alleviate daily burden for families while potentially decreasing reliance on resource-intensive OFCs.7, 8 Even partial tolerance (e.g., to baked or partially cooked egg) can yield meaningful improvements in diet variety and quality of life. Our study has limitations. Its retrospective design introduces potential selection and information biases. Single-centre scope and small sample size may limit generalisability. Univariate testing was the primary focus to best utilize our sample size and avoid overfitting. Additionally, it is an ideal first test to assess for a clinically promising tool. The multivariate COX regression analysis had a limiting event to variable ratio of 7 and caution should be taken when interpreting this result. However, with the independent nature of age, dietetic input and peanut allergy as variables as well as the narrow confidence interval produced, it was a useful analysis to include. Component testing panels were limited to ovomucoid and ovalbumin. Broader CRD profiling might reveal patterns not captured here. Future work should include prospective, multicentre cohorts with serial CRD to evaluate whether dynamic changes (e.g., SpIgE trajectories) better correlate with ladder progression than baseline values. This may provide a prognostic benefit of CRD's. While unfeasible in many study environments, a randomized comparison of ladder strategies versus avoidance with timed OFCs would clarify whether ladders accelerate resolution or simply track natural history while improving lived experience. In summary, baseline component testing did not predict egg ladder outcomes in our cohort of young children with IgE-mediated egg allergy. However, larger studies are required, especially reviewing ovomucoid as a prognosticator. Given the absence of prognostic utility, we discourage relying on component SpIgE at diagnosis to forecast ladder success. The egg ladder remains a practical, family-centred approach of treating egg allergy. Priorities for research include identifying dynamic biomarkers and standardizing ladder pathways. M.L., S.H., D.G. and J.T. conceived the study, M.L. and D.G. collected data, M.L. and R.V. completed formal analysis, M.L. and S.H. wrote original draft and D.G., M.C., C.T., A.G., R.V. and J.T. reviewed and edited the manuscript. The authors have no conflicts of interest to declare. There was no funding obtained for this project. For transparency, the peer review documents associated with this article are available at https://doi.org/10.1111/pai.70353. Research data are not shared.
Lane et al. (Wed,) studied this question.