allergy - uwa

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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 [email protected] PATH2220 2017

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Page 1: ALLERGY - UWA

Path2220 INTRODUCTION TO HUMAN DISEASE

ALLERGY

Dr. Erika BosioResearch Fellow – Centre for Clinical Research in

Emergency Medicine,

Harry Perkins Institute of Medical Research

University of Western Australia

[email protected]

2017

Page 2: ALLERGY - UWA

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

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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.

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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.

Hypersensitivity

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Hypersensitivity Reactions

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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.

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ALLERGYMay 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

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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

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Symptoms of Allergy: Digestive Tract

• Diarrhea

• Constipation

• Nausea and Vomiting

• Abdominal bloating and distension

• Abdominal pain

• Indigestion (heartburn)

• Belching

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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)

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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…….

Page 12: ALLERGY - UWA

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

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The mechanism of Allergy

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Development of An Allergy

Larche M, et al. Nature Immunol Rev 2006

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There are two phases to the Allergic Response…..

Classic Allergic Reaction

Flushing

Hypotension

Increased mucus production

Pruritus

Smooth muscle contraction

Vascular leakage

Late –phase Reaction

Eosinophil infiltration

Neutrophil infiltration

Fibrin deposition

Mononuclear infiltration

Tissue destruction

Minutes Hours

https://i1.wp.com/www.wellapalooza.com/wp-content/uploads/2015/09/Human_mast_cell.jpg

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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

Page 17: ALLERGY - UWA

Mast Cell Inflammatory Mediator Release

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Common Allergic Disorders

• Allergic rhinitis

• Asthma

• Atopic eczema

• Food Allergy

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Allergy: Rhinitis, Eczema & Conjunctivitis

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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 adivalent 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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Page 22: ALLERGY - UWA

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 recurrentepisodes of wheezing, chest tightness, breathlessness andcough 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 responsivenessto a variety of stimuli.

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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

Page 24: ALLERGY - UWA

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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Asthma

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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

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Food Allergy

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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

Page 30: ALLERGY - UWA

Food Allergy ?

Source: http://www.allergycentre.com.my/index.html

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Food Allergy - Triggers

Egg

Cow’s milk

Peanut *

Tree Nuts *

Seafood *

Sesame *

Soy

Fish

Wheat

* These tend to be

life-long

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Food Allergy: Symptom Severity

Mild – Moderate: Swelling of face, lips and/or eyesSkin hivesAbdominal pain, vomiting

Severe (Anaphylaxis) Difficulty/noisy breathingTongue swellingThroat swelling/tightness Difficulty talking / Hoarse voice Wheeze or persistent coughPersistent dizziness and/or collapsePale and floppy (young children)

Peanuts Tree nuts Shellfish MilkEgg

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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

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Laboratory DiagnosisFor 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.30.1.2008. testing.

http://en.wikipedia.org/wiki/File:Aller

gy_skin_testing.JPG

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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 antigen-specific IgE.

Page 36: ALLERGY - UWA

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).