Paediatrics (RCH) - Theses
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ItemExploring the investigation, diagnosis and clinical management of tree nut and peanut allergy in children( 2023-03)By the age of one, 1 in 10 Australian children have developed a food allergy. Most people are aware of common allergens such as cow’s milk, egg, and peanut, but tree nut allergy is less recognised and researched despite having a prevalence similar to peanut allergy in older children. Peanut and tree nuts are responsible for the majority of fatal or near-fatal allergic reactions to food and with natural allergy resolution for peanut reported as 30%, and tree nuts collectively reported as 10%, a diagnosis of peanut or tree nut allergy carries a poor prognosis. Diagnosis of food allergy is not simple. Clinical history determines whether a clinician may perform a diagnostic test such as a skin prick test or blood test to determine the likelihood of allergy. If the result is not conclusive, then an oral food challenge (OFC), or medically supervised food introduction is required to achieve an accurate diagnosis. Whilst OFCs are the gold standard for diagnosis, they are time and labour intensive, expensive and put the individual at risk of severe allergic reaction, or anaphylaxis. They are also the ‘bottle-neck’ in the diagnostic process with limited access relative to the burden of food allergy assessments. With limited understanding of the accuracy of current diagnostic tools there is a real risk for over-diagnosis of tree nut and peanut allergy. This thesis aims to improve the diagnostic approach to tree nut and peanut allergy. It explores several areas involved in the diagnosis of tree nut and peanut allergy including describing the prevalence of cashew allergy and the diagnostic accuracy of currently used tests for specific tree nuts. It also explores the use of diagnostic algorithms as a method to improve diagnostic accuracy and reduce the need for OFCs in both modelled and ‘real world’ datasets for cashew and peanut allergy. The cost of these interventions is also assessed in the first economic evaluation for use of diagnostic algorithms in tree nut allergy diagnosis. Using the population-based EarlyNuts cohort (n=1933), I found the prevalence of cashew allergy in 1 year old infants to be 1.49%, with sensitisation (SPT result >/= 3mm) seen in 1.96%. Infants with eczema in the first year of life were more likely to be cashew allergic (adjusted odds ratio=5.75) and there was also an association between peanut allergy and cashew allergy (adjusted odds ratio=19.30). Cashew was introduced before 12 months of age in 25% of participants, which was low compared to other foods such as peanut. I have undertaken a systematic review of the accuracy of the current tests used in diagnosing tree nut allergy. This review highlighted that for some tree nuts, such as cashew or walnut, the accuracy of tests was reasonable, but many nuts lacked evidence about a conclusive diagnostic cut-off, increasing the likelihood of requiring an OFC for definitive diagnosis. Tests for cashew allergy were most accurate compared to other tree nuts, and newer blood tests, specifically IgE to the cashew component ana o 3, were superior to the commonly used method of a cashew skin prick test for diagnosis. To investigate this further, I combined and analysed global data from studies of patients with possible cashew allergy that had data on both test results and food challenge outcomes, demonstrating that using ana o 3 or a diagnostic algorithm incorporating sIgE to cashew followed by ana o 3 resulted in an 80% reduction in the need for an OFC to get a definitive diagnosis compared to skin prick testing alone. I performed a cost-comparison analysis comparing these approaches to skin prick testing alone (the current clinical practice standard in Australia) again using modelled data. This demonstrated a 46% cost reduction to the healthcare system. The final step of my PhD was to investigate the clinical and economic impact of a similar 2-step algorithm used in a large tertiary hospital allergy department for diagnosis of peanut allergy. This retrospective clinical audit (n=8826) demonstrated an uptake of the diagnostic algorithm of 41.95% of eligible presentations, which resulted in a 27.8% reduction in OFCs performed compared to using peanut SPT alone. I also demonstrated a 32% cost reduction as a result of implementing this pathway. The outcomes of my thesis can be directly translated into modifications of clinical practice resulting in significant clinical impact by achieving more accurate and timely clinical outcomes with fewer OFCs, improved safety for individuals and substantial cost reductions to the health system.