Respiratory- Allergic disease Flashcards
a) Give an overview of Gel and Coomb’s classification of hypersensitivity.
b) Which type is involved in allergic diseases?
a) Type 1: Immediate hypersensitivity
Type 2: Direct cell killing
Type 3: Immune complex mediated
Type 4: Delayed type hypersensitivity
b) Type 1: immediate hypersensitivity
Define allergy
IgE-mediated antibody response to external antigen.
What is the hygeine hypothesis?
A suggestion for why the prevalence of allergy in the Western world is increasing.
General decrease in infectious burden in early life (in particular, respiratory infections) and variations in GI flora results in increased predispositions to allergic conditions during childhood.
How quickly does type 1 hypersensitivity occur after exposure to an antigen?
Minutes- 1-2 hours
What are some generic features of type 1 allergic response?
Quick onset
Responses are stereotyped
May be associated with more than one organ system
Presentation is influenced by site of contact
Threshold for reaction may be influenced by cofactors such as alcohol, exercise and infection.
List some allergens
House dust mite Pollen and animal dander Foods Drugs Latex Bee and wasp venom
Which cells and molecules are involved in type 1 allergic response?
B lymphocytes: Recognise antigen
Produce antigen-specific IgE antibody
T lymphocytes: provide help for B cells to make IgE
Mast cells: release vasoactive substances
Where are Mast cells found?
Resident in tissues, especially at interface with external environment.
What are the vasoactive substances released by Mast cells?
Which of these are preformed and which are synthesised on demand?
Preformed: Histamine, tryptase and heparin
Synthesised on demand: Leukotrienes, prostaglandins, cytokines, including IL4 and TNF
What is the function of Mast cells?
They are important in defence against parasites and wound healing.
Describe the role of Mast cells in allergic reactions.
Mast cells express receptors for the Fc region of IgE on their surfaces.
On encounter with an allergen, B cells produce specific IgE antibodies for that allergen.
The allergen is cleared and residual IgE bind to mast cells via Fc receptors, from which there is no great consequence.
On re-encounter with the allergen, the allergen binds to IgE coated Mast cells, and the Mast cell membrane is disrupted.
There is then release of vasoactive substances from the mast cells, such as hitamine, tryptase and heparin, and there is increased transcriptino of Leukotrienes and cytokines.
Name some clinical features of allergic disease.
Within minutes of vasoactive substance release, clinical manifestations occur: Urticaria Angioedema Asthma Allergic rhinitis and conjunctivitis Anaphylaxis
What is the difference between extrinsic and intrinsic asthma?
Extrinsic asthma is a response to an external allergen, and is IgE mediated.
Intrinsic asthma is non-allergic, and is not IgE mediated.
Name some triggers of allergic asthma.
house dust mite, grass pollen, animal dander.
It is also associated with other allergic disease.
What happens when there is a release of histamine and other inflammatory mediators in the lung?
Muscle spasm: causes bronchoconstriction (manifests clinically as wheeze)
Mucosal inflammation: causes mucosal oedema and increases secretions (manifests clinically as sputum production)
Inflammatory cell infiltrate: infiltration of lymphocytes and eosinophils into bronchioles (manifests clinically as yellow sputum)
List a number of other names for urticaria
Hives
Wheals
Nettle rash
Blisters
What is angioedema?
Self-limited, localised swelling of subcutaneous tissues and mucous membranes.
It is non-pitting oedema, and is not itchy unless associated with urticaria.
What are the clinical features of anaphylaxis?
Angioedema of lips and mucous membranes Laryngeal obstruction and stridor Hypotension (due to vasodilation) Oral itching vomiting diarrhoea abdominal pain Itch of palms, soles of feet and genitalia Wheeze, bronchoconstriction Flushing and urticaria Conjunctival infection Rhinorrhea Feeling of impending doom Loss of consciousness Death Cardiac arrhythmias Myocardial infarct
What are the three groups of people who die from anaphylaxis?
Those who do not know they are allergic to the allergen
Severe asthmatics
People who don’t carry their epipen
Are all allergic-type diseases mediated by IgE?
No- sometimes there can be idiopathic reactions where there is spontaneous degranulation of Mast cells.
The mast cells are “twitchy”
Name some non-allergic causes of Mast cell degranulation
Drugs: morphine and other opiates, NSAIDs
Thyroid disease
Idiopathic
Physical urticaria: urticaria in response to pressure or heat
a) Which common drug can induce asthma?
b) What proportion of asthmatics does this affect?
c) What characterises this reaction?
a) Aspirin.
b) About 20%
c) A wheeze 0.5- 3 hours after ingestion
Triggered by aspirin as well as other classical NSAIDs, e.g. diclofenac and ibuprofen.
Paracetamol and COX2 inhibitors are generally ok.
What is Samter’s triad?
Asthma, nasal polyps and salicylate sensitivity
It affects 2-3% of asthamtics
It may require dietary modification because of the high prevalence of salicylates in some foods
What are generic features of an IgE mediated reaction to ask about when taking an allergy history?
Reactions occurs soon (minutes to 1-2 hours) after exposure to allergen
Responses are consistent
Often associated with more than one organ system involved (e.g. urticaria, angioedema, rhinits etc)
What are some specific investigations for an allergy?
Elective investigations:
Skin prick test
Quantitate specific IgE to putative allergen
Challenge test- supervised exposure to putative allergen
Can also look for evidence of mast cell degranulation during an acute anaphylactic episode - can look for serum mast cell tryptase levels
a) What is the gold standard test to support a diagnosis of allergy?
b) How is this test carried out?
c) What can affect the test result, and how can this problem be avoided?
a) Skin prick test
b) The patient is exposed to a standardised solution of allergen extract through a skin prick to the forearm. A positive reaction is a local wheal and flare response.
c) Drugs can affect the response. Antihistamines should be discontinued for at least 48 hours before testing.
Corticosteroids do not influence the result.
Describe specific IgE testing.
When is this test useful?
The amount of IgE in the serum directed against a specific allergen is measured.
Sensitivity and specificity is about 70-75% compared with skin prick test.
It is useful when skin prick test is unavailable, e.g if the patient is on antihistamines and has such severe disease that they cannot come of them.
Why is it not useful to measure total IgE when making a diagnosis of allergic disease?
Allergic disorders are the most common cause of a raised total IgE in industrial societies, but there are many other causes of a raised IgE, such as vasculitis, lymphome, drugs.
Significant allergic disease can also occur in the absence of an elevated IgE.
How do you test for anaphylaxis?
Detection of mast cell tryptase in the serum.
In anaphylaxis, serum tryptase reaches a peak concentration in about 1-2 hours and returns to baseline by about 6 hours.
This can be used to test for anaphylaxis because a rise in tryptase only occurs in anaphylaxis, and not in local reactions.
List ways to manage IgE mediated allergic disorders.
Allergen avoidance Block mast cell activation Prevent effects of mast cell activation Anti-inflammatory agents Management of anaphylaxis Immunotherapy
Describe a way of blocking mast cell activation.
Using mast cell stabilisers such as sodium cromoglycate.
These stabilise mast cell membranes.
They have poor oral absorption, but can be used as a topical spray (e.g. nasal) when allergen exposure is predictable.
E.g. hayfever and exercise induced asthma.
Describe how you can prevent the effects of mast cell activation
- Antihistamines: H1 receptor antagonists
Mainstay of treatment in allergic disease
Block the effects of histamine
Newer agents are more specific and cause less sedation
Useful prophylactically and to control symptoms - Leukotriene receptor antagonists:
Block the effects of leukotrienes which are synthesised by mast cells after activation
e.g. Montelukast
Describe how you can manage allergic disorders using anti-inflammatory agents
Corticosteroids: Anti-inflammatory Inhibits the formation of many different inflammatory mediators: Platelet activating factor Prostaglandins Cytokines
What is the management of anaphyaxis?
Patients carry self-injectable adrenaline
It acts on B2 adrenoceptors to constrict arterial smooth muscle
This increases blood pressure thereby limiting vascular leakage, and dilates bronchial smooth muscle limiting airflow obstruction.
Describe immunotherapy used to manage allergic disorders.
What are the risks of this type of therapy?
There is controlled exposure to increasing amounts of the allergen.
There are subcutaneous injections of tiny amounts of the allergen, followed by gradual increase in dose.
Mechanism of action is unknown.
It may lead to inhibition of anaphylaxis.
Risks: Anaphylaxis
