1. Allergy and Allergic Diseases Incidence steadily rising Trebling in the last 20 years 1/ /3 of the population will develop clinical allergic condition Amongst the highest rates in the World Costs – Quality of Life issues 3 million consultations costing £300 million; 70,000 Admissions costing £80 million; £1 billion drugs expenditure

2. Food Allergy Atopic Eczema Dermatitis Allergic Rhinitis Asthma Age “The Atopic March” Infancy Toddlers School Age Allergic Diseases – adverse, heightened immunological responses (hypersensitivity) to external agents Anaphylaxis Acute Urticaria

4. Allergic disease prevalence Asthma X 6 in Children X 3-4 in Adults Population Prevalence 12 – 15% Atopic Dermatitis Allergic Rhinitis Food Allergy …also increasing Anaphylaxis… 7-fold

5. Asthma / Allergic Disease Genetics Strong Genetic Association Cytokine genes – IL-4, IL-5, IL-10, TGF-  IgE receptor genes LPS responsiveness genes Skin barrier function genes - fillagrin Twin Concordance 75% 1 affected parent - 40% 2 Affected Parents - 60% Same Disease - Even Higher … but genes do not explain the growing prevalence

6. Asthma Prevalence Vs GNP per capita; adapted from ISAAC study Asthma Epidemiology West Germany Vs East Germany Prevalence Studies Inverse relationship with: Family Size Family Order Day Care in Early Years Outside the Home Place of residence – Farm / Animal exposure Vs City Socioeconomic factors

7. The Hygiene Hypothesis Centers for Disease Control, Atlanta Less Infectious Diseases More Antibiotic Use Better Sanitation Western Countries … Promotion of Allergic Immune Responses

8. The Infant Immune System T H 2 Bias All Infants TH1TH1 Increasing Age T H 1-mediated diseases are also increasing X2 Multiple Sclerosis X3 Crohn’s Disease T H 1 and T H 2 diseases co- exist in many patients

9. Regulatory T T H 2 Bias All Infants TH1TH1 Increasing Age IL-4, IL-5, IL-13 TNF-  ; IFN-  ; IL-10; TGF  Controlled Inflammation The Infant Immune System – Normal Maturation

10. Allergy Investigation HISTORY Laboratory tests (RASTs) / in-vivo – skin testing – IgE-dependent Challenges – Useful; Experienced; Monitored setting Usefulness – Disease / Interpreter Alternative testing – no basis in logic

11. Allergy Management Anti-Inflammatory Treatments Corticosteroids Leukotriene Inhibitors Anti-histamines Effector Antagonists  -2 agonists Adrenaline Allergen Avoidance Variable effects  disease

12. Allergy Management cont./ Immune Manipulation Conventional Immunosuppression Variable Not Widespread Allergen Desensitization Therapy / Immunotherapy Molecular engineering Allergen sequencing IgG4 / TGF-  production T H Redirection M. Vaccae Probiotic therapies Allergen / Cytokine / CpG motif Conjugate “Vaccines”

13. Allergy Management cont. 2/ Anti-IgE Therapy Stopping the Cascade Humanised Mouse MAb Omalizumab Asthma Reduced steroid use; hospitalization; rescue treatments Reduced IgE; IgE Receptor FDA Approval 2003 Incorporation in Asthma Guidelines

14. +/ - Stridor; Breathing / Speaking Difficulty; Hypotension; Collapse; GI Symptoms ANAPHYLAXIS

15. Epidemiology Sharp increase Under-reported 30 – 950 / 100,000 / year – US meta-analysis 0.5 – 2.0% lifetime prevalence 1 / 12 / year recur UK – 75 / 100,000 / year Fatalities – 1 / 2.5 million / year; lower in children

16. Triggers Potentially anything – careful history Commonest - Foods – peanuts; Other tree nuts; fish and shellfish; milk Venoms – wasp, bee Drugs – penicillins; anaesthetics; ASA and NSAIDs; ACEIs Other Medical – Contrast media; Latex

17. Why Does This Happen? Foods peanut; egg; milk; seafoods Drugs penicillins; suxamethonium; Mabs Latex Venoms

19. Adrenaline Autoinjectors UK Resuscitation Council Guidelines Irish Consensus Document from IGI – IMJ Jan 2008 –Definite –Anaphylaxis in Asthma –Limited access to care –Trace amount triggers –Severe hypotension ( venoms) –Probably –High incidence of Severe reactions ( nuts / shellfish) –Comorbidities –No –Asthma alone; positive skin tests alone; clear avoidable trigger; positive family history

20. Food Sensitivity and Other Allergic Disorders Does Food Allergy Cause Other Conditions? Atopic Eczema Co-existence of conditions High Frequency of RAST / PST Positivity Severe > Mild; Younger > Older Exclusions Challenges Asthma Severe acute reactions Early food allergy positively predicts later asthma Younger > Older Consider in difficult asthma Urticaria

21. Asthma / Allergy Prevention Early Allergen Exposure Food allergen avoidance / Breastfeeding - food allergy prevention -Other allergic disorders ? Exposure to allergens in infancy e.g. house dust mite; food antigens; pollens --  IgE production Early food exposure as a preventative in at risk infants? Conflicting evidence re: pet exposure RESEARCH