allergy - uwa
TRANSCRIPT
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
2017
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
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.
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
Hypersensitivity Reactions
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.
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
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
Symptoms of Allergy: Digestive Tract
• Diarrhea
• Constipation
• Nausea and Vomiting
• Abdominal bloating and distension
• Abdominal pain
• Indigestion (heartburn)
• Belching
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)
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…….
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
The mechanism of Allergy
Development of An Allergy
Larche M, et al. Nature Immunol Rev 2006
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
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
Mast Cell Inflammatory Mediator Release
Common Allergic Disorders
• Allergic rhinitis
• Asthma
• Atopic eczema
• Food Allergy
Allergy: Rhinitis, Eczema & Conjunctivitis
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”
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.
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
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
Asthma
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
Food Allergy
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
Food Allergy ?
Source: http://www.allergycentre.com.my/index.html
Food Allergy - Triggers
Egg
Cow’s milk
Peanut *
Tree Nuts *
Seafood *
Sesame *
Soy
Fish
Wheat
* These tend to be
life-long
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
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
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
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.
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).