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Allergy and Allergic Diseases

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

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Allergy and Allergic Diseases

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

  3. 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

  4. 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

  5. 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 • Place of residence – Farm / Animal exposure Vs City Asthma Prevalence Vs GNP per capita; adapted from ISAAC study

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

  7. TH1 TH2 Bias • All Infants Increasing Age • TH1-mediated diseases are also increasing • X2 Multiple Sclerosis • X3 Crohn’s Disease • TH1 and TH2 diseases co-exist in many patients The Infant Immune System

  8. TH1 TH2 Bias • All Infants Increasing Age Regulatory T TNF-a; IFN-g; IL-10;TGF-b IL-4, IL-5, IL-13 The Infant Immune System – Normal Maturation Controlled Inflammation

  9. 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

  10. Corticosteroids • Leukotriene Inhibitors • Anti-histamines Anti-Inflammatory Treatments Effector Antagonists • b-2 agonists • Adrenaline Allergen Avoidance • Variable effects a disease Allergy Management

  11. 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”

  12. 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

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

  14. 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

  15. 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

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

  17. 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

  18. Urticaria 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

  19. Asthma / Allergy Prevention • 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 Early Allergen Exposure

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