Path2220 INTRODUCTION TO HUMAN DISEASE ALLERGY. Dr. Erika Bosio

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1 Path2220 INTRODUCTION TO HUMAN DISEASE ALLERGY Dr. Erika Bosio Research Fellow Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research University of Western Australia PATH

2 OBJECTIVES To understand: The basic principles of type I allergic disease The definitions of allergic rhinitis and asthma The pathogenesis of early and delayed reactions The clinical features of food allergy

3 What is Allergy? The inappropriate reaction of the immune system to a substance (allergen) in the environment, which is usually harmless (e.g. pollen, animal dander, dust mite, food) or bites, stings and medications. Type of hypersensitivity reaction of the immune system (There are 4 of these). Allergy may involve more the one type of reaction.

4 Hypersensitivity Hypersensitivity (hypersensitivity reaction) refers to undesirable immune reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. Hypersensitivity reactions: four types; based on the mechanisms involved and time taken for the reaction, a particular clinical condition (disease) may involve more than one type of reaction.

5 Hypersensitivity Reactions

6 What is an Allergic Reaction? The development of symptoms following exposure to an allergen eg. hives, swelling of the lips, eyes or face, vomiting or wheeze. Allergic reactions can be IgE or non-ige-mediated and range from mild to severe. Anaphylaxis is the most severe form of allergic reaction.

7 ALLERGY May affect up to 20% of people Allergic reaction can be provoked by: Ingesting nuts, shellfish, eggs Inhaling substances like pollen, dust, animal dander, moulds and mildew Skin contact with plants, chemicals Insect stings

8 Symptoms of Allergy: Skin and Mucous Membranes Atopic dermatitis (eczema) Urticaria (hives) Angioedema (swelling of tissues, especially mouth and face) Pruritus (itching) Contact dermatitis (rash in contact with allergen) Oral symptoms (irritation and swelling of tissues around and inside the mouth) Oral allergy syndrome

9 Symptoms of Allergy: Digestive Tract Diarrhea Constipation Nausea and Vomiting Abdominal bloating and distension Abdominal pain Indigestion (heartburn) Belching

10 Symptoms of Allergy: Respiratory Tract Seasonal or perennial rhinitis (hayfever) Rhinorrhea (runny nose) Allergic conjunctivitis (itchy, watery, reddened eyes) Serous otitis media (earache with effusion) [ gum ear ; glue ear ] Asthma Laryngeal oedema (throat tightening due to swelling of tissues)

11 Symptoms of Allergy: Nervous System Migraine Other headaches Spots before the eyes Listlessness Hyperactivity Lack of concentration Tension-fatigue syndrome Irritability Chilliness Dizziness and many many more.

12 Anaphylaxis Severe reaction of rapid onset, involving most organ systems, which results in circulatory collapse and drop in blood pressure In the most extreme cases the reaction progresses to anaphylactic shock with cardiovascular collapse This can be fatal

13 The mechanism of Allergy

14 Development of An Allergy Larche M, et al. Nature Immunol Rev 2006

15 There are two phases to the Allergic Response.. Minutes Classic Allergic Reaction Flushing Hypotension Increased mucus production Pruritus Smooth muscle contraction Vascular leakage Hours Late phase Reaction Eosinophil infiltration Neutrophil infiltration Fibrin deposition Mononuclear infiltration Tissue destruction za.com/wpcontent/uploads/2015/09/human_ mast_cell.jpg

16 CLASSIFICATION OF ALLERGIC REACTIONS Immediate - (< 1 hour) - anaphylaxis, hypotension, laryngeal edema, urticarial/angioedema, wheezing Accelerated - (1- < 72 hours) - urticaria, angioedema, laryngeal edema, wheezing Late (> 72 hours) - rash, serum sickness, cytopenias or haemolytic anemia, drug fever, hypersensitivity (organ involvement) IgE Non-IgE

17 Mast Cell Inflammatory Mediator Release

18 Common Allergic Disorders Allergic rhinitis Asthma Atopic eczema Food Allergy

19 Allergy: Rhinitis, Eczema & Conjunctivitis

20 Allergic Rhinitis - Definition Condition associated with inflammation of the nasal mucosa due to immunological hypersensitivity to environmental allergens, leading to nasal irritation, rhinorrhoea and nasal obstruction Mediated by degranulation of mast cells and eosinophils Degranulation triggered by: Cross-linking of IgE antibodies bound to mast cell by a divalent hapten Cross-linking of IgE by anti-ige Effects felt within minutes of exposure Also known as Immediate hypersensitivity or Allergy

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22 Asthma - Definition Chronic inflammatory disorder of the airways Many cell types play a role, in particular mast cells, eosinophils, and T-lymphocytes. In susceptible individuals this inflammation causes recurrent episodes of wheezing, chest tightness, breathlessness and cough particularly at night and/or in the early morning. These symptoms are associated with airflow limitation that is at least partly reversible either spontaneously or with treatment. The inflammation causes an increase in airway responsiveness to a variety of stimuli.

23 Airway Inflammation Early event in asthma Primarily allergen mediated, some contribution from other environmental factors (pollution, smoking etc) 3 components: Infiltration of cells Change in resident cells Changes in the non cellular components of the airway wall

24 Airway Inflammation Cellular Infiltration: Eosinophils and CD4+ lymphocytes infiltrate the airway wall Th2 T lymphocytes predominate, secreting IL-3, -4, -5, GMCSF IgE production Promotes allergic inflammation

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26 Asthma

27 Pathogenesis of Asthma - Chronic Changes Airflow limitation Chronic mucus plug formation persistent airflow limitation in severe intractable asthma Airway remodeling irreversible component of airflow limitation secondary to structural airway matrix changes

28 Food Allergy

29 Food Allergy: How Common Is It? Occurs in 1/20 children and 2/100 adults 10% of children up to 1y.o. 4-8% of children aged up to 5y.o. 2% of adults

30 Food Allergy? Source:

31 Food Allergy - Triggers Egg Cow s milk Peanut * Tree Nuts * Seafood * Sesame * Soy Fish Wheat * These tend to be life-long

32 Food Allergy: Symptom Severity Mild Moderate: Swelling of face, lips and/or eyes Skin hives Abdominal pain, vomiting Severe (Anaphylaxis) Peanuts Tree nuts Shellfish Milk Egg Difficulty/noisy breathing Tongue swelling Throat swelling/tightness Difficulty talking / Hoarse voice Wheeze or persistent cough Persistent dizziness and/or collapse Pale and floppy (young children)

33 Food Allergy: Factors Affecting Symptom Severity Severity of allergy Amount eaten Form of the food Liquid may be absorbed faster Whether eaten on its own or with other foods Exercise around the same time as meal may worsen severity Whether food is raw or cooked cooked? better tolerated Presence or absence of asthma Menstrual cycle in females Alcohol intake

34 Laboratory Diagnosis For IgE-mediated allergy; by skin test and blood test The cutaneous test (prick test, puncture test, epicutaneous test) Routine diagnosis in diseases (atopic or anaphylactic). A single drop of concentrated aqueous allergen extract placed on the skin which is then pricked lightly with a needle point at the center of the drop. After 20 minutes the reaction is graded and recorded Wolfgang Ihloff. Allergy skin testing. gy_skin_testing.jpg

35 Laboratory Diagnosis Blood tests IgE levels may be elevated in patients who are atopic, but the level does not necessarily correlate with clinical symptoms. The tryptase level can be elevated, which is indicative of mast cell degranulation. False-negative results can occur. An elevated eosinophil count may be observed in patients with atopic disease. RAST/CAP RAST/ImmunoCAP: measures antigenspecific IgE.

36 Prevention Avoid triggers such as foods and medications, that have caused an allergic reaction, even a mild one. This includes detailed questioning about ingredients when eating away from home. Ingredient labels should also be carefully examined. A medical ID tag should be worn by people who know that they have serious allergic reaction. If any history of a serious allergic reactions, carry emergency medications (Epipen - epinephrine).