Background
Egg allergy (EA) is one of most common food allergies that may occur very early in life 1,2. In 2011, Koplin et al3 and other studies reported that the prevalence of food allergies in 1-year-old children is as high as 11%, including 8.9% raw egg allergy,. A birth cohort study involving 12,049 infants in 9 European countries found that the highest incidence of egg allergy confirmed by the open food stimulation test was 2.18% in the UK1. In China, there cross-sectional studies4 spanning 20 years (1999,2009 and 2019) on infants in the southeast city of Chongqing reported that the incidence of IgE- mediated food allergies has risen from 3.5% to 7.7% and 7.6%in 2019, and that egg and milk are the most common food allergies in childhood in China 5.
In 2012,a multicenter study showed that egg was the first allergen in the food allergy test of 0-2-year-old children in China, and its history and clinical manifestations were mainly skin symptoms (85-96.3%)6.Immunoglobulin E (IgE)-mediated EA,aggravated AD symptoms in infancy that main manifestations are infantile eczema combined with digestive system and respiratory system issues, which affect the growth, development, and quality of the child’s daily life,however, eggs are also one of the main sources of dietary protein for infants and young children, which drives EA with AD become a common skin complaint, and how to reduce blindly avoiding eggs also a challenge for pediatricians. Although natural tolerance occurs in 49.3% of infants with an average age of 3 years 7-9, Lack of relevant literature research in China,the exact age bracket of tolerance and predictive factors remain to be determined.
Mechanistically, five protein components in egg white (EW) have been found to bind with human serum IgE to induce an allergic reaction, including ovomucoid (OVM or Gal D 1), ovalbumin (OVA or Gal D 2), ovotransferrin (OVT or Gal D 3), lysozyme (Gal D 4), and ovomucin. In addition, egg yolk (EY) also contains antigens associated with allergies, namely yolk phosvitin,and yolk glycoprotein 42 (YGP42, Gal D 6) 10-11 . Because of the different antigenic components, clinical egg allergy is divided into three states—EW allergy (EWA), EY allergy (EYA), and whole egg allergy (WEA)12.In this study, egg yolk and egg white oral food challenge test (OFC) were respectivd,identification of these three states and exploration of the probable factors that predict clinical outcomes may provide management strategies for EAs. Methods
Patients Selection
This study was approved by the Ethics Committee of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, and was conducted in accordance with the Declaration of Helsinki.All patients provided written informed consent before inclusion in the study.From the pediatric allergy clinic of Ruijin Hospital, China, 200 children with AD aged 6 months to 2.5 years old were included in the present study from 2018 to 2019.IgE-mediated EA was defined by OFC.,firetly,a positive skin prick test (SPT) to EW or EY ≥ 3 mm and by keeping a diet diary,children whose AD symptoms(sleep status, itching, rash area and exudation) and digestive tract symptoms improved significantly with the elimination of the whole egg were further evaluated by OFC .The antigen used in the SPT included those fresh food obtained from egg yolk, egg white, cow’s milk, wheat, fish, shrimp, peanut,soybean.
Oral Food Challenges
The child added egg yolk (boiled at 100°C for 15 min) in stepwise-increasing doses given every 30 min, if no reaction was observed with the previous dose.,OFC was performed in the hospital by a trained pediatrician, and the subjects were observed for at least 2 hours after the last dose before going home. Parents were asked to report any symptoms that occurred in the following at least 3 days. If any reactions suspicious of EA were reported, the children were to be brought to the hospital for appropriate manageent immediately inaccordance with the EAACI guidelines13.And next,the egg white OFC was performed again after elimination of whole egg for 2 weeks..Any participant with an incomplete diagnostic process was considered a dropout.The symptoms were improved after avoidance, and the symptoms reappeared as OFC positive after re-intake, and the diagnosis of egg allergy was established. On the contrary, it is negative.
Groups
The children with AD who had negative results from both tests were recruited into the AD group(as control subjects).The Scoring Atopic Dermatitis (SCORAD) score and pruritus (itchy skin)/sleep Visual Analogue Scale (VAS) score were used to evaluate the clinical baseline skin conditions.The 78 children with EA were divided into three subgroups as follows: 7 with only EYA (OnlyEYA), 20 with only EWA (OnlyEWA), and 51 with whole egg allergy (WEA).At the end of follow-up, the patients with egg allergy were divided into tolerance group and persistent allergy group.
Follow up
Children with atopic dermatitis are given routine treatment, including skin moisturizing / or glucocorticoid ointment (topical application).Children diagnosed with egg ingredient allergy strictly avoid the corresponding ingredients, including oral food intake and family living environment contact avoidance.All patients were followed up at 3, 6, 12, and 18 months by recording the SCORAD score, itching/sleep VAS score, and respiratory symptoms (including nasal symptoms, chronic cough, wheezing, and asthma diagnosed by clinicians). SPT was concurrently conducted in the EA group. Tolerance is defined with negative in OFC: a wheal < 3 mm and no allergic reaction after ingesting egg yolk or egg white for 3 consecutive days,OFC was also performed in the hospital by a trained pediatrician; otherwise, persistent allergy is considered.
Statistical analysis
SPSS v 25 (IBM Corp., Armonk, NY, USA) was used for statistical analyses. The Mann–Whitney and χ2 tests were used to compare the characteristics of the tolerant and persistent groups. Taking the egg tolerance as the dependent variable, univariate and multivariate logistic regression analyses were conducted, and the risk factors were used to plot the receiver operating characteristic (ROC) curves. Each cutoff value was calculated using the Youden index to obtain the prediction model. The survival analysis using the Kaplan–Meier curve was used to determine whether the predictor could effectively predict tolerance development.