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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 Allergic Diseases – adverse, heightened immunological responses (hypersensitivity) to external agents “The Atopic March” Food Allergy Infancy Atopic Eczema Dermatitis Toddlers Allergic Rhinitis Age Asthma School Age Anaphylaxis Acute Urticaria 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 Asthma / Allergic Disease Genetics • Strong Genetic Association Cytokine genes – IL-4, IL-5, IL-10, TGF-b 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 Asthma Epidemiology Socioeconomic factors •West Germany Vs East Germany Prevalence Studies Inverse relationship with: • Family Size •Family Order •Day Care in Early Years Outside the Home Asthma Prevalence Vs GNP per capita; adapted from ISAAC study •Place of residence – Farm / Animal exposure Vs City The Hygiene Hypothesis Western Countries •Less Infectious Diseases •More Antibiotic Use •Better Sanitation Centers for Disease Control, Atlanta … Promotion of Allergic Immune Responses The Infant Immune System TH2 Bias •All Infants TH1 Increasing Age •TH1-mediated diseases are also increasing X2 Multiple Sclerosis X3 Crohn’s Disease •TH1 and TH2 diseases coexist in many patients The Infant Immune System – Normal Maturation TH2 Bias •All Infants TH1 Increasing Age Regulatory T IL-4, IL-5, IL-13 TNF-a; IFNg; IL-10; TGF-b Controlled Inflammation 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 Allergy Management Anti-Inflammatory Treatments •Corticosteroids •Leukotriene Inhibitors •Anti-histamines Effector Antagonists b-2 agonists •Adrenaline Allergen Avoidance •Variable effects a disease Allergy Management cont./ Immune Manipulation •Conventional Immunosuppression Variable Not Widespread •Allergen Desensitization Therapy / Immunotherapy Molecular engineering Allergen sequencing IgG4 / TGF-b production •TH Redirection M. Vaccae Probiotic therapies Allergen / Cytokine / CpG motif Conjugate “Vaccines” Allergy Management cont. 2/ Anti-IgE Therapy •Humanised Mouse MAb Omalizumab •Asthma Reduced steroid use; hospitalization; rescue treatments Reduced IgE; IgE Receptor FDA Approval 2003 Incorporation in Asthma Guidelines Stopping the Cascade ANAPHYLAXIS +/ - Stridor; Breathing / Speaking Difficulty; Hypotension; Collapse; GI Symptoms 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 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 Why Does This Happen? Foods peanut; egg; milk; seafoods Drugs penicillins; suxamethonium; Mabs Latex Venoms 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 Food Sensitivity and Other Allergic Disorders • Does Food Allergy Cause Other Conditions? • Asthma • Severe acute reactions • Early food allergy positively predicts later asthma • Younger > Older • Consider in difficult asthma • Urticaria • Atopic Eczema • Co-existence of conditions • High Frequency of RAST / PST Positivity • Severe > Mild; Younger > Older • Exclusions • Challenges Asthma / Allergy Prevention •Food allergen avoidance / Breastfeeding - food allergy prevention -Other allergic disorders ? Early Allergen Exposure •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