Nutritional strategies for allergy prevention, diagnosis and treatment, with a specific focus on egg allergy

Abstract

Food allergy affects up to 10% of Australian children. This thesis addresses questions related to the prevention, diagnosis, and management of food allergy, specifically focusing on egg allergy. The results of a systematic review investigating the relationship between whole foods in the maternal diet during pregnancy and lactation and development of atopic disorders (including egg allergy) in childhood are reported. No widespread or consistent links were identified; however dietary patterns with high Mediterranean diet scores, diets rich in fruits and vegetables, fish, and vitamin D containing foods were suggestive of benefit, requiring further evaluation. From the results of this review, the management of allergy was of particular interest, and this thesis focuses on egg allergy as it the most common food allergy affecting Australian children. A literature review of skin prick testing (SPT), serum-specific IgE (sIgE) levels and oral food challenge (OFC) protocols used to diagnose and manage egg allergy highlighted heterogeneity in terms of testing reagents, and the type of egg, dosing rates and total dose used for OFCs. Development of standard egg OFC protocols will facilitate consistent clinical care and comparison between studies reporting outcomes of OFCs. Egg protein is a complex glycoprotein and its structure and allergenicity is affected by heating. OFCs using fresh egg are common; however, to limit the risk of foodborne infection, some allergy units use pasteurised raw egg. Pasteurisation may affect the structure and allergenicity of egg proteins, and this was assessed by comparing binding of serum IgE from egg allergic children to pasteurised whole raw egg powder with fresh whole raw egg. The main egg allergens were present in pasteurised whole raw egg powder, and serum IgE of egg-allergic children bound to them in a similar pattern to those in fresh whole raw egg, indicating that pasteurised whole raw egg powder is a suitable substitute for raw egg in clinical practice for OFCs. Extensively heated (baked) egg is tolerated by a majority of egg allergic children before they tolerate less well cooked forms of egg and consumption of baked egg (BE) is associated with immunological changes suggestive of evolving tolerance to all forms of egg. However, there are no RCTs that directly test if the natural history of childhood egg allergy is altered by inclusion of BE in the diet. Studies reporting the effects of BE in the diet of BE tolerant, egg allergic children were not randomised and controlled, and used retrospective comparator groups. The rationale, development, conduct and outcomes of an RCT examining the clinical and immunological effects of ingestion of BE in 1 to 5 year old egg allergic children are reported. The results of this study suggest that tolerance to BE may be indicative of a phenotype of egg allergy that is outgrown, and this may not be influenced by consumption of BE for six months. Egg white SPT and sIgE levels do not accurately predict BE tolerance, and a BE OFC is recommended to assess tolerance to BE. Using the opportunistic sample of children screened for the trial the utility of whole egg, egg yolk, ovomucoid and ovalbumin SPT, sIgE and whole egg IgG4 testing to predict the outcome of BE OFCs were compared with testing to egg white. The results of this investigation indicated that whole egg and ovalbumin sIgE testing may predict tolerance to BE more accurately than other egg allergens, however no one test was ideal, and a combination of measures may be required. A BE OFC remains the gold standard for determining tolerance to BE. This thesis strengthens the evidence base for standard protocols for management of IgE mediated egg allergy in children, and provides important information regarding influences of the perinatal maternal diet and atopy development.