1. Allergic Disease

2. Atopy The predisposition to produce high quantities of Immunoglobulin (Ig)-E Immediate (Type I hypersensitivity) Mast cells, basophils, eosinophils, Th2 cells

3. Allergic Disease Seen in 30-35% of the population Perennial & seasonal allergic rhinitis Allergic (extrinsic asthma) Atopic and contact dermatitis Urticaria Food intolerance

4. Allergy Elevated IgE levels seen in allergy and parasitic infection Binds to mast cells and basophils Often specific for harmless environmental factors - allergens

5. Allergic rhinitis Seasonal (pollen, spores) or perennial (house dust mite) Mucus production (Runny nose, nasal stuffiness Itching & sneezing Treat with antihistamines or nasal steroids

6. Urticaria Wheal and flare Itching Allergen-induced Idiopathic – pressure, cold etc. Food – shellfish, strawberries, peanuts Treat with antihistamines

7. Atopic dermatitis Allergen –induced particularly milk protein from the gut enters blood stream –deposited in skin – mast cell degranulation Exfoliating eczema and itching Treat with antihistamines May progress to asthma

8. Anaphylaxis Very acute and severe reaction to allergen Peanuts, shellfish, penicillin, insect stings Allergen moves from gut to blood stream Massive histamine release from mast cells and basophils Vasodilatation leads to dramatic drop in blood pressure Often fatal if not treated with adrenaline

9. Allergens Environmental substances Usually benign Sub-group of individuals exhibit a hypersensitivity reaction (type 1)

10. Allergens Mite faeces (digestive enzymes) Pollen Animal dander (cats) Insect stings Food

11. Mast cells Release pre-formed mediators (histamine) and lipids together with several TH2 cytokines

12. Histamine Skin – wheal, erythema, pruritis Eye - conjunctivitis, erythema, pruritis Nose – nasal discharge, sneeze, pruritis Lung – bronchospasm of smooth muscle

13. Histamine Therapeutic intervention in allergy often focused on blocking the effects of histamine Histamine also functions as a neurotransmitter in CNS Very important in maintaining a state of arousal or awareness

14. First Generation Antihistamines The first H1 antagonist synthesised by Bovet & Staub at the Institut Pasteur Too weak or toxic Phenbezamine first effective antihistamine Mepyramine maleate, diphenhydramine & tripelennamine developed in 1940’s Still in use today

15. First Generation Antihistamines Easily cross the blood–brain barrier. Sedative and anticholinergic effects (sedating antihistamines). Short half-lives. Limited use in the treatment of allergic symptoms. Still widely used, mainly as over-the-counter products, often in combination with other drugs.

16. Second Generation Antihistamines Highly effective treatments for allergic disease Do not cross blood-brain barrier Lack significant CNS & anticholinergic effects Long half life Among the most frequently prescribed and safest drugs - expensive

17. Other treatments Nasal steroids – must be given before season – relieve nasal blockade Antihistamines combined with anti-leukotriene drugs Avoidance -mattress covers, specialised Hoovers, wood floors,