Resolution of egg allergy occurs in the majority of egg allergic children. Positive specific IgE antibodies to ovomucoid (OVM) have been suggested to be of greater predictive value for persistent egg allergy than specific IgE to egg white. The performance of OVM-specific IgE antibody levels in a cohort of children referred for a routine egg challenge was compared with egg white specific IgE levels in predicting a positive egg challenge. 24/47 subjects had persistent egg allergy. Receiver operating characteristic analysis showed that OVM-specific IgE testing was the most useful test for the diagnosis of persistent egg allergy. The optimal decision points for the prediction of persistent egg allergy were >0.35
Egg allergy is common in early childhood, affecting 1-2% of all preschool children and may be associated with severe symptoms, including anaphylaxis [
The gold standard for the diagnosis of egg allergy is the double-blind placebo-controlled food challenge (DBPCFC) which is both resource and time expensive, and potentially hazardous [
Children (2–16 years old) attending the Paediatric Allergy Clinics at Bristol Royal Hospital for Children from July 2009 to February 2010 with egg allergy previously confirmed by positive history and positive SPT or specific IgE to hen egg and clinically suspected of having outgrown their egg allergy were recruited. Children with an inconclusive clinical history were excluded as were those with the absence of previously documented specific IgE to egg white or positive SPT. The study protocol was approved by the Ethics Committee of North Somerset and South Bristol, UK. Written informed consent was obtained from the parent of each subject.
Serum concentrations of specific IgE antibodies (sIgE) to OVM and egg white, and total IgE were measured at the clinic visit. Skin prick test responses to egg white were also measured. All eligible children subsequently had an oral egg provocation challenge (OPC). Figure
Pathway of subjects through the study.
Specific IgE concentrations in venous blood to egg white (EW) and ovomucoid (OVM) were measured using ImmunoCap (Phadia AB, Uppsala, Sweden).
Allergen skin prick tests were performed by a single, trained paediatric allergy nurse using a commercial one-prick lancet technique on the volar aspect of the forearm. Commercially available extracts of egg white using a 1 : 20 (wt/vol) solution (Soluprick, ALK, Uppsala, Sweden) were used with histamine dihydrochloride (10 mg/mL, ALK-Abello A/S, Horsholm, Denmark) as a positive control and saline (Soluprick SQ, ALK-Abello) as a negative control. The maximal skin wheal diameter (mm) was measured after 15 minutes.
Based on the OPC, children who reacted were classified as having persistent egg allergy and children tolerant of egg throughout the challenge were classified as having resolved egg allergy.
An SPT reaction was considered positive if the resultant wheal was >3 mm in diameter in the presence of a reaction to histamine of at least 3 mm in diameter and a negative response to the corresponding negative control. Specific IgE antibody levels ≥0.35
The likelihood of a positive OPC following a positive reaction in each of three screening tests: SPT to egg white; raised specific IgE levels to egg white; raised specific IgE levels to ovomucoid, were compared. Fagan’s nomogram was used to calculate post-test probability [
Forty-seven children, aged 2–16 years (median 4.6 years; 19 girls) were recruited and completed an egg OPC. All children had been under annual review in the allergy clinic following their initial presentation and had remained on an egg-free diet since diagnosis. Twenty-four children (51%) had a positive challenge; 10 (42%) reacted to extensively heated egg, 13 (54%) tolerated extensively heated egg but not freeze-dried powdered egg, and 1 reacted to raw egg. Twenty-three children with no response to OPC were classed as resolved food allergy.
Figure
Sensitisation to hen’s egg white.
EW SPT and specific IgE levels and OVM-specific IgE levels in children with extensively heated egg allergy (EHE), freeze-dried, or raw egg allergy (FDR) and resolved egg allergy (R).
Univariate logistic regression showed an odds ratio for a positive egg OPC following a positive SPT as 2.7 (CI: 1.50–4.81), following a positive sIgE level for egg white was 3.3 (CI: 0.89–12.26) and following a positive sIgE level for ovomucoid as 7.4 (CI: 1.61–34.00).
Figure
Test | Area under the curve (95% confidence interval) | Sensitivity | Specificity |
---|---|---|---|
SPT egg white | 0.88 (0.77–0.99) | 75% | 100% |
sIgE egg white | 0.92 (0.85–1.00) | 96% | 70% |
sIgE ovomucoid | 0.94 (0.85–1.00) | 96% | 78% |
Receiver-operator characteristic curves showing the performance of the three screening tests in children with persistent and resolved egg allergy in predicting any form of egg allergy.
This study showed a SPT wheal diameter ≥3 mm to egg white to be very highly predictive of persistent egg allergy, although it could not be used to distinguish children who could tolerate extensively heated eggs from those who could not. However, skin test specificity was poor with 6 children (25%) with persistent allergy having a negative SPT result. A positive specific IgE level to ovomucoid had a greater positive predictive value and increased post-test probability of persistent egg allergy than specific IgE to egg white. Children who could not tolerate cooked egg had significantly higher specific IgE levels to both egg white and ovomucoid than children with resolved egg allergy or those able to tolerate extensively heated egg.
The SPT results in this study concur with the work of Sampson and Ho who reported a 3 mm SPT wheal diameter to have high sensitivity but a low specificity and therefore to be of limited clinical value. Diagnostic specific IgE cut-off levels in this study have been reported using 95% positive predictive values to establish decision points [
Published cut-off specific IgE levels for ovomucoid, as for egg white, vary considerably between the few available studies. Cut-off values are higher in published studies than reported in this paper. Ando et al. reported that a cut-off value of 11
Lemon-Mulé and co-workers found regular ingestion of heated egg in egg allergic children was associated with immunological changes including a reduction in skin prick test wheal diameters to egg white. Specifically, continued ingestion of heated egg was associated with a reduction in ovalbumin-specific IgE levels and an increase in ovalbumin-specific and ovomucoid-specific IgG4 levels [
Therapeutic strategies for food allergy are currently of great interest, with particular focus upon oral desensitisation to foods. Recent evidence suggests that diets containing extensively heated egg may be an effective method of oral desensitisation, making clarification of each child’s egg allergic status of increased importance [
The strengths of this study lie in the well-characterised clinic population. All food challenges were performed using the same protocol and supervised by one individual for consistency. SPT was performed by a single trained clinical nurse specialists reducing interoperator variability. A limitation of this study was the difference in composition of the two subgroups for children with persistent egg allergy, which makes the data difficult to compare with previously published studies. Most previous studies report a large number of children with raw egg allergy, which were not observed in this study. Additionally many studies have focused on atopic prognostic factors which have not been examined closely in this study. Factors of potential interest, including information on the number of previous reactions, were also not recorded. This study only included children over the age of 2 years due to recognised differences in specific IgE levels and SPT wheal diameters in infants and children to enable more precise data analysis, and all children had previous confirmation of their egg allergy rather than just positive IgE results. This varies from some previous studies where definitive confirmation has not been required.
This study has shown a clear difference in median specific ovomucoid IgE levels between children with extensively heated egg allergy and children only reacting to freeze-dried or raw egg. The optimal decision points for predicting that a child would have an allergic reaction to extensively heated egg on OPC with at least 95% certainty were 10
In a group of children from a tertiary allergic clinic, measurement of specific IgE antibodies for ovomucoid was the best test for the prediction of persistent egg allergy. The use of skin testing as a basis for deciding to perform an OPC is limited without the additional information provided by specific IgE testing. The recommendations of this study are that specific IgE to ovomucoid should be used as an allergen marker prior to referring a child for an egg OPC test. However, despite improved screening, there remain a number of children in whom it is not possible to know whether a child has outgrown their egg allergy who will continue to need to be challenged in a safe environment.
This study was supported by an educational grant from the Florence Nightingale Foundation.