Immunology Flashcards
Criteria for likely anaphylaxis?
An anaphylactic reaction is highly likely when the following 3 criteria are fulfilled:
Sudden onset and rapid progression of symptoms
Life-threatening Airway and / or Breathing and / or Circulation problems
Skin and/or mucosal changes (flushing, urticaria, angioedema)
Paediatric dosage of IM adrenaline to treat anaphylaxis?
1mg/mL (1:1000) concentration
> 12 years: 500 micrograms (0.5mL)
6-12 years: 300 micrograms (0.3mL)
6 months - 6 years: 150 micrograms (0.15mL)
Under 6 months: 100-150 micrograms (0.1-0.15)
Non shockable rhythms
Asystole
Pulseless Electrical Activity (PEA)
What is meant by allergy/allergen?
Allergy is an umbrella term for hypersensitivity of the immune system to allergens.
Allergens are proteins that the immune system recognises as foreign and potential harmful, leading to an allergic immune response.
These proteins are types of antigen.
Antigens are proteins that can be recognised by the immune system.
The body will come in contact with millions of different antigens, and very few will lead to a hypersensitivity reaction.
The ones that do are called allergens.
What is atopy?
Atopy is a term used to describe a predisposition to having hypersensitivity reactions to allergens.
It refers to the tendency to develop conditions such as eczema, asthma, hayfever, allergic rhinitis and food allergies.
These conditions are referred to as atopic conditions.
Patients often have more than one atopic condition, and atopy frequently runs in families.
The Importance of Establishing and Excluding Allergies
Having a food allergy can be a huge psycho-social burden, particularly in those who have anaphylaxis or an epipen. It means checking all food labels for ingredients, ensuring all those responsible for the child are aware (e.g. school, other parents and relatives) and being very cautious or avoiding eating out in restaurants or anywhere with unlabelled food, where allergens may have made their way into foods.
It is not uncommon for symptoms and histories of “allergy” to actually be a somatisation disorder rather than a true allergy. It is important to establish whether symptoms are down to an allergy, or more psychological, because an allergy diagnosis can lead to restrictive or unhealthy eating and do more harm than good. Allergy testing can play a role in reassuring patients that they do not have a true allergy to certain foods.
The skin sensitisation theory is currently the leading theory on the origin of allergies. This theory suggests which contributors to a child developing an allergy to a food?
- There is a break in the infant’s skin (from eczema or a skin infection) that allows allergens, such as peanut proteins, from the environment to cross the skin and react with the immune system.
- The child does not have contact with that allergen from the gastrointestinal tract, and there is an absence of GI exposure to the allergen.
The theory is that allergens entering through the skin are recognised by the immune system as being foreign and harmful proteins. The immune system reacts by becoming sensitised to that allergen, so that when it next encounters that allergen again it will launch a full immune response (an allergic reaction).
When a baby is weaned at around 6 months, if they are regularly eating foods that contain that allergen, their GI tract is regularly being exposed to that protein. The GI tract will recognise that allergen as a food and not a foreign or harmful protein, and inform the immune system that it is a safe thing to be exposed to.
The theory is that regular exposure to an allergen through food and preventing exposure to that allergen through the skin barrier can help prevent food allergies developing.
Examples of conditions that are due to hypersensitivity reactions?
Asthma
Atopic eczema
Allergic rhinitis
Hayfever
Food allergies
Animal allergies
The Coombs and Gell classification is used to describe the underlying pathology of different hypersensitivity reactions - what is meant by Type 1?
IgE antibodies to a specific allergen trigger MAST CELLS and BASOPHILS to release HISTAMINES and OTHER CYTOKINES
This causes an IMMEDIATE reaction
Typical food allergy reactions, where exposure to the allergen leads to an acute reaction, range from itching, facial swelling and urticaria to anaphylaxis.
The Coombs and Gell classification is used to describe the underlying pathology of different hypersensitivity reactions - what is meant by Type 2?
IgG and IgM antibodies react to an allergen and activate the COMPLEMENT SYSTEM, leading to direct damage to the local cells.
Examples are haemolytic disease of the newborn and transfusion reactions.
The Coombs and Gell classification is used to describe the underlying pathology of different hypersensitivity reactions - what is meant by Type 3?
IMMUNE COMPLEXS accumulate and cause damage to local tissues.
Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Henoch-Schönlein purpura (HSP)
The Coombs and Gell classification is used to describe the underlying pathology of different hypersensitivity reactions - what is meant by Type 4?
CELL MEDIATED hypersensitivity reactions caused by T LYMPHOCYTES.
T-CELLS are inappropriately activated, causing inflammation and damage to local tissues. Examples are organ transplant rejection and contact dermatitis.
Type 1 hypersensitivity reaction example
Anaphylaxis
Asthma
Type 2 hypersensitivity reaction example
haemolytic disease of the newborn and transfusion reactions.
Type 3 hypersensitivity reaction example
Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Henoch-Schönlein purpura (HSP)
Type 4 hypersensitvity reaction example
Examples are autoimmune conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Henoch-Schönlein purpura (HSP)
Important areas to cover in allergy history?
Timing after exposure to the allergen
Previous and subsequent exposure and reaction to the allergen
Symptoms of rash, swelling, breathing difficulty, wheeze and cough
Previous personal and family history of atopic conditions and allergies
What are the three main ways to test for allergy?
Skin prick testing
RAST testing, which involves blood tests for total and specific immunoglobulin E (IgE)
Food challenge testing
Strengths and weaknesses of various allergy tests?
Skin prick testing and RAST testing assess sensitisation and not allergy.
This is important, because it makes these tests notoriously unreliable and misleading.
They often come back showing that the patient is sensitised to many of the things you have tested for, and it becomes very challenging to explain to the child or their parents that the positive test results do not mean it is unsafe for the child to eat those foods.
Food challenge testing is the gold standard investigation for diagnosing allergy, however it requires a lot of time and resources and is only available in selected places.
Gold standard investigation for allergy diagnosis?
Food challenge
What does skin prick testing entail?
A patch of skin is selected, usually on the patients forearm.
Strategic allergen solutions are selected, for example peanuts, house dust mite and pollen.
A drop of each allergen solution is placed at marked points along the patch of skin, along with a water control and a histamine control.
A fresh needle is used to make a tiny break in the skin at the site of each allergen.
After 15 minutes, the size of the wheals to each allergen are assessed and compared to the controls.
How is patch testing performed and when is it useful?
Patch testing is the most helpful in determining an allergic contact dermatitis in response to a specific allergen. It is not helpful for food allergies. This could be for latex, perfumes, cosmetics or plants. A patch containing the allergen is placed on the patient’s skin.
The patch can either contain a specific allergen, or a grid of lots of allergens as a screening tool.
After 2 – 3 days the skin reaction to the patch is assessed.
What does RAST testing involve?
RAST testing measures the total and allergen specific IgE quantities in the patient’s blood sample. In a patient with atopic conditions such as eczema and asthma, the results will often come back positive for everything you test.
What does a food challenge involve?
A food challenge should be performed in a specialised unit with very close monitoring.
The child is gradually given increasing quantities of an allergen to assess the reaction, starting with almost non-existent quantities diluted further in other foods, for example mixing a small amount of peanut into a bar of chocolate.
Children are monitored very closely after each exposure.
This can be very helpful in excluding allergies for reassurance.
Allergy management?
Establishing the correct allergen is essential
Avoidance of that allergen
Avoiding foods that trigger reactions
Regular hoovering and changing sheets and pillows
in patients that are allergic to house dust mites
Staying in doors when the pollen count is high
Prophylactic antihistamines are useful when contact is inevitable, for example hayfever and allergic rhinitis
Patients at risk of anaphylactic reactions should be given an adrenalin auto-injector
In certain cases, specialist centres may initiate a lengthy process of gradually exposing the patients to allergens over months, called immunotherapy, with the aim of reducing their reaction to certain foods or allergens.
Management of allergic reaction
- Antihistamines (e.g. cetirizine)
- Steroids (e.g. oral prednisolone, topical hydrocortisone or IV hydrocortisone)
- Intramuscular adrenalin in anaphylaxis
Antihistamines and steroids work by dampening the immune response to allergens. Close monitoring is essential after an allergic reaction to ensure it does not progress to anaphylaxis.
What is anaphylaxis, and what causes it?
Anaphylaxis is a life-threatening medical emergency.
It is caused by a severe type 1 hypersensitivity reaction.
Immunoglobulin E (IgE) stimulates mast cells to rapidly release histamine and other pro-inflammatory chemicals.
This is called mast cell degranulation.
This causes a rapid onset of symptoms, with airway, breathing and/or circulation compromise.
The key feature that differentiates anaphylaxis from a non-anaphylactic allergic reaction is what?
compromise of the airway, breathing or circulation.
Presentation on anaphylaxis?
Patients present with a history of exposure to an allergen (although it can be idiopathic).
There will be rapid onset of allergic symptoms:
- Urticaria
- Itching
- Angio-oedema, with swelling around lips and eyes
- Abdominal pain
Additional symptoms that indicate anaphylaxis are:
- Shortness of breath
- Wheeze
- Swelling of the larynx, causing stridor
- Tachycardia
- Lightheadedness
- Collapse
Once a diagnosis of anaphylaxis is established, what three medications given to treat the reaction?
Intramuscular adrenalin, repeated after 5 minutes if required
Antihistamines, such as oral chlorphenamine or cetirizine
Steroids, usually intravenous hydrocortisone
Anaphylaxis A-E
A – Airway: Secure the airway, once diagnosis established (ie. respiratory distress/haemodynamic compromise/airway compromise) give IM Adrenalin 1/1000 0.5ml
B – Breathing: Provide oxygen if required. Salbutamol can help with wheezing.
C – Circulation: Provide an IV bolus of fluids
D – Disability: Lie the patient flat to improve cerebral perfusion
E – Exposure: Look for flushing, urticaria and angio-oedema
Anaphylaxis - management post event
All children should have a period of assessment and observation after an anaphylactic reaction, as biphasic reactions can occur, meaning they can have a second anaphylactic reaction after successful treatment of the first. Children should be admitted to the paediatric unit for observation.
Anaphylaxis can be confirmed by measuring the serum mast cell tryptase within 6 hours of the event. Tryptase is released during mast cell degranulation and stays in the blood for 6 hours before gradually disappearing.
Education and follow-up of the family and child is essential. They need to be educated about allergy, how to avoid allergens and how to spot the signs of anaphylaxis. Parents should be trained in basic life support. Specialist referral should be made in all children with anaphylaxis for diagnosis, education, follow up and training in how to use an adrenalin auto-injector.
How can you confirm anaphylaxis after the event?
Anaphylaxis can be confirmed by measuring the serum mast cell tryptase within 6 hours of the event.
Tryptase is released during mast cell degranulation and stays in the blood for 6 hours before gradually disappearing.
Epipen, Jext and Emerade are trade names for what?
Adrenalin auto-injector devices.
Indications for an Adrenalin Auto-Injector?
They are given to all children and adolescents with anaphylactic reactions.
They may also be considered in children with generalised allergic reactions (without anaphylaxis) with certain risk factors:
- Asthma requiring inhaled steroids
- Poor access to medical treatment (e.g. rural locations)
- Adolescents, who are at higher risk
- Nut or insect sting allergies are higher risk
- Significant co-morbidities, such as cardiovascular disease
How to Use an Adrenalin Auto-Injector
The first step is to confirm the diagnosis of anaphylaxis.
Prepare the device by removing the safety cap on the non-needle end. There is a blue cap on EpiPen and a yellow cap on Jext.
Grip the device in a fist with the needle end pointing downwards. The needle end is orange on EpiPen and black on Jext. Do not put your thumb over the end, because if the device is upside down you will inject your thumb with adrenalin and could risk losing it.
Administer the injection by firmly jabbing the device into the outer portion of the mid thigh until the device clicks. This can be done through clothing. EpiPen advise holding it in place for 3 seconds and Jext advise 10 seconds before removing the device.
Remove the device and gently massage the area for 10 seconds.
Phone an emergency ambulance. A second dose may be given (with a new pen) after 5 minutes if required.
How long after the first dose of adrenalin should the second dose be given if required?
5 minutes
What is allergic rhinitis and why does it occur?
Allergic rhinitis is a condition caused by an IgE-mediated type 1 hypersensitivity reaction.
Environmental allergens cause an allergic inflammatory response in the nasal mucosa.
It is very common and can significantly affect sleep, mood, hobbies, work and school performance and quality of life.
