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

Food Allergy

Atopic Eczema Dermatitis

Allergic Rhinitis

AsthmaAge

“The Atopic March”

Infancy

Toddlers

School Age

Allergic Diseases – adverse, heightened immunological responses (hypersensitivity) to external agents

Anaphylaxis Acute Urticaria

Allergic disease prevalence

• AsthmaX 6 in ChildrenX 3-4 in Adults

Population Prevalence 12 – 15%

Atopic Dermatitis Allergic Rhinitis Food Allergy …also increasingAnaphylaxis… 7-fold

Asthma / Allergic Disease Genetics

• Strong Genetic AssociationCytokine genes – IL-4, IL-5, IL-10, TGF-

IgE receptor genesLPS 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 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

The Hygiene Hypothesis

Centers for Disease Control, Atlanta

•Less Infectious Diseases

•More Antibiotic Use

•Better Sanitation

Western Countries

… Promotion of Allergic Immune Responses

The Infant Immune System

TH2 Bias •All Infants TH1

Increasing Age

•TH1-mediated diseases are also increasing

X2 Multiple SclerosisX3 Crohn’s Disease

•TH1 and TH2 diseases co-exist in many patients

Regulatory T

TH2 Bias •All Infants TH1

Increasing Age

IL-4, IL-5, IL-13 TNF-; IFN-; IL-10; TGF

Controlled Inflammation

The Infant Immune System – Normal Maturation

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-2 agonists•Adrenaline

Allergen Avoidance•Variable effects disease

Allergy Management cont./

Immune Manipulation •Conventional ImmunosuppressionVariable

Not Widespread

•Allergen Desensitization Therapy / ImmunotherapyMolecular engineering

Allergen sequencingIgG4 / TGF-production

•TH RedirectionM. Vaccae

Probiotic therapiesAllergen / Cytokine / CpG motif Conjugate “Vaccines”

Allergy Management cont. 2/

Anti-IgE Therapy Stopping the Cascade

•Humanised Mouse MAb

Omalizumab

•AsthmaReduced steroid use;

hospitalization; rescue treatments

Reduced IgE; IgE Receptor

FDA Approval 2003Incorporation in

Asthma Guidelines

+/ - Stridor; Breathing / Speaking Difficulty; Hypotension; Collapse;

GI Symptoms

ANAPHYLAXIS

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?

Foodspeanut; egg; milk;

seafoodsDrugs

penicillins; suxamethonium; MabsLatex

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?

• 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

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

productionEarly food exposure as a

preventative in at risk infants?

•Conflicting evidence re: pet exposure

•RESEARCH