Allergic Disease

Atopy• The predisposition to produce high quantities of

Immunoglobulin (Ig)-E

• Immediate (Type I hypersensitivity)

• Mast cells, basophils, eosinophils, Th2 cells

Allergic Disease

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

Allergy

• Elevated IgE levels seen in allergy and parasitic infection

• Binds to mast cells and basophils• Often specific for harmless

environmental factors - allergens

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

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

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

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

Allergens

• Environmental substances

• Usually benign

• Sub-group of individuals exhibit a hypersensitivity reaction (type 1)

Allergens

Mite faeces (digestive enzymes)

Pollen

Animal dander (cats)

Insect stings

Food

Mast cells 

Release pre-formed mediators (histamine) and lipids together with several TH2 cytokines

Histamine

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

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

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

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.

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

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,