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Thursday 12 November 2015


'How allergies develop through the cutaneous route and tolerance through the oral route'

Professor Lack (Kings College, London)


Mice can become allergic to food molecules such as ovalbumin through inflamed or abraded skin, whereas single doses of oral antigen induced tolerance and prevents them from becoming allergic.  On that basis the Dual Allergen Exposure Hypothesis was suggested in 1998 (Lancet 1998 Nov 7;352(9139):1557) which posits that sensitisation to foods occur in babies with an inflamed skin barrier and that tolerance to food proteins is induced orally by early exposure to food antigens.  A study of more than 10,000 schoolchildren in Israel and the UK (with similar ancestral backgrounds) showed that the rate of peanut allergy was 10 times higher in UK children who avoided peanuts compared to Israeli children who displayed almost no peanut allergy and who started consuming peanuts early in the first year of life (J Allergy Clin Immunol. 2008 Nov;122(5):984-91). 

The induction of oral tolerance as a strategy to prevent allergies was conclusively confirmed in the large and definitive randomised controlled trial known as LEAP (Learning Early About Peanut), recently published in the New England Journal of Medicine (N Engl J Med. 2015 Feb 26;372(9):803-13).  This showed that early introduction of peanut into the diet of high-risk infants with severe eczema between 4-11 months of age reduced the development of peanut allergy by 86% compared to those who excluded peanut. The EAT (Enquiring About Tolerance) study is currently being concluded in a group of 1300 children where half are consuming egg, milk, peanut, fish, wheat, and sesame as of three months of age with the aim being to reduce the overall burden of food allergic disease compared to babies who are exclusively breast fed for the first 6 months of life. 

There is circumstantial evidence for cutaneous sensitisation to foods in humans.  In a large prospective infant cohort study in 2003 (N Engl J Med. 2003 Mar 13;348(11):977-85) the development of peanut allergy was strongly associated with early infantile eczema and exposure to emollients on the skin that contained peanut oil.  It was subsequently shown by both Food Frequency Questionnaires (J Allergy Clin Immunol. 2009 Feb;123(2):417-23) and the measurement of environmental peanut in the home that high levels of peanut in the environment was associated with an increased risk of developing peanut allergy in children who had eczema or in children who had filaggrin mutations which reduced skin barrier function (J Allergy Clin Immunol. 2014 Oct;134(4):867-875,  J Allergy Clin Immunol. 2015 Jan;135(1):164-70).


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