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BSc INTRODUCTION TO ALLERGY JANUARY 2003. INTRODUCTION TO ALLERGY. A Clinical Perspective. THE IMMUNE SYSTEM. Essential for a normal healthy life Main function is to protect us against infection Think of the benefits of immunisation Sometimes the immune system can “go wrong”.

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introduction to allergy

INTRODUCTION TO ALLERGY

A Clinical Perspective

the immune system
THE IMMUNE SYSTEM
  • Essential for a normal healthy life
  • Main function is to protect us against infection
  • Think of the benefits of immunisation
  • Sometimes the immune system can “go wrong”
the immune system can go wrong in several ways
THE IMMUNE SYSTEM CAN GO WRONG IN SEVERAL WAYS
  • Gell and Coomb’s classification of hypersensitivity
  • “Allergy” is the commonest way that the immune system can go wrong
gell and coomb s classification of the hypersensitiviy states
GELL AND COOMB’S CLASSIFICATION OF THE HYPERSENSITIVIY STATES
  • TYPE 1 - Immediate, IgE mediated, anaphylactic
  • TYPE 2 - Cytotoxic
  • TYPE 3 - Immune complex
  • TYPE 4 - Delayed type hypersensitivity
examples of ige mediated allergy
EXAMPLES OF IgE MEDIATED ALLERGY
  • Hay fever – running eyes and nose during the pollen season
  • Asthma – attack might be brought on by contact with eg a cat
  • Peanut allergic patient may develop swelling of lips and a rash
how common is allergy
HOW COMMON IS ALLERGY?
  • Nearly half of all young adults show evidence in blood that they have the potential to develop this kind of allergy
  • Many of these people remain symptom free
other names for this type of allergy
OTHER NAMES FOR THIS TYPE OF ALLERGY
  • Type 1 allergy
  • IgE mediated allergy
  • Immediate type allergy
  • Atopy
slide22

People who suffer from Hay fever, asthma,and some types of eczema, usually have an immune system that reacts in an inconvenient way to one or more common substances in the environment

slide23

Antibody combining sites

Light chains

IgE

Kappa or lambda

εHeavy chains

  • Defence against parasites
  • Causes allergies
  • Small amounts in serum
  • Cytophilic to mast cells

IgG

IgM

IgA

IgE

IgD

Fc

Mast Cell

ige mediated allergy immunology 2
IgE MEDIATED ALLERGY - IMMUNOLOGY (2)

Y

Y

IgE

Y

Y

Some people produce IgE as well as the other classes of antibody.

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

ige mediated allergy immunology 3
IgE MEDIATED ALLERGY - IMMUNOLOGY (3)

Y

Y

Y

Y

Y

Y

Y

Y

IgE is a “cytophilic” antibody. It attaches itself to

mast cells in the tissues and basophils in the blood

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

Y

ige mediated allergy immunology 4
IgE MEDIATED ALLERGY - IMMUNOLOGY (4)

Y

Y

Y

sensitised mast cell

Sensitised mast cells are harmless, however, they contain little granules of chemical messengers. These are not harmless when released into the circulation.

Y

Y

Y

Y

Y

ige mediated allergy immunology 5
IgE MEDIATED ALLERGY - IMMUNOLOGY (5)

Y

Y

Y

sensitised mast cell

The chemicals are not released into the circulation unless the IgE antibody surrounding the mast cell meets its antigen.

Y

Y

Y

Y

Y

ige mediated allergy immunology 6
IgE MEDIATED ALLERGY - IMMUNOLOGY (6)

Y

Y

Y

sensitised mast cell meeting antigen

Message is sent into mast cell telling it to degranulate and to start producing new chemicals

Y

Y

Y

Y

Y

ige mediated allergy immunology 7
IgE MEDIATED ALLERGY - IMMUNOLOGY (7)

Y

Y

mast cell degranulates

Y

Chemical messengers are released into the vicinity and some carried in the circulation.

Y

Y

Y

Y

Y

ige mediated allergy immunology 8
IgE MEDIATED ALLERGY - IMMUNOLOGY (8)

Histamine:

Y

Y

Y

Histamine is the main chemical messenger but there are others

Constricts bronchioles

Y

Dilates blood vessels

Y

Y

Increases vascular permeability

Y

Y

ige mediated allergy immunology 9
IgE MEDIATED ALLERGY - IMMUNOLOGY (9)

Late response:

This is largely due to attraction of eosinophils to the site and the release of active substances from them.

Prolonged mucous secretion

Oedema

Persistent bronchial hyper-response

types of t helper cells
Types of t-helper cells

IgE

Y

TH2

Y

Y

Y

Y

Y

Some people produce IgE as well as the other classes of antibody.

Y

Y

Y

Y

Y

P

Y

Y

Y

Y

Y

TH1

B

ige mediated allergy
IgE mediated allergy

IgE

Y

TH2

Y

Y

Y

Y

Y

Some people produce IgE as well as the other classes of antibody.

Y

Y

Y

Y

Y

P

Y

Y

Y

Y

Y

TH1

B

th1 cells
TH1 cells
  • Produce gamma interferon
  • Produce tumour necrosis factor
  • Important in macrophage activation and phagocytic responses
  • Important in development of cell mediated immunity
th2 cells
TH2 CELLS
  • Produce interleukins 4,5,10,13
  • Important in inhibition of macrophage activation
  • Important in the the development of IgE responses
  • Important in development of eosinophilia
t helper cell priming
T-helper cell priming
  • Determined by cytokine milieu
  • IL-12 leads to TH1 responses
  • IL-4 leads to TH2 responses
cytokines in allergy
Cytokines in allergy
  • TH2 cytokines
  • IL-4 and IL-13 are essential to regulation of IgE class switching
  • IL-5 is necessary for the differentiation, recruitment and activation of eosinophils
t helper cells in infancy
T- Helper cells in infancy
  • Infant thought to have a TH2 bias
  • Gradually diminishes during first two years of life in non allergic individual
  • Associated with maturing of IL-12 production
  • In allergic infants, reverse occurs
  • Is a TH1 stimulus necessary from the environment to avoid the development of allergic disease ?
effect of infections
Effect of Infections
  • Many bacterial infections enhance TH1
  • Many viral infections enhance TH1
  • Measles enhances TH2
  • Helminths enhance TH2 strongly
what is anaphylaxis
WHAT IS ANAPHYLAXIS?
  • Anaphylaxis is the most severe form of IgE mediated allergy that exists
  • It is an immediate life-threatening reaction that requires urgent treatment
the urgency of anaphylaxis
THE URGENCY OF ANAPHYLAXIS
  • The urgency of anaphylaxis is such that a patient could die before qualified help is available
  • It is very important therefore, that patients and also their relatives and know how to observe and if necessary give treatment before symptoms become life-threatening.
fortunately
Fortunately…
  • The severest form of anaphylaxis is very uncommon
  • Anaphylaxis responds very well to treatment with adrenaline
  • Death from anaphylaxis is very rare.
examples of substances that cause anaphylaxis
EXAMPLES OF SUBSTANCES THAT CAUSE ANAPHYLAXIS
  • FOOD eg peanuts, tree nuts, cow’s milk, eggs, shellfish, legumes, fruits
  • Bee and wasp stings
  • Natural latex rubber
  • Medications such as antibiotics and anaesthetic agents
slide57

An individual may have numerous allergies but if they are unfortunate enough to have anaphylaxis, it is usually to one substance only

is it always possible to identify a cause of anaphylaxis
IS IT ALWAYS POSSIBLE TO IDENTIFY A CAUSE OF ANAPHYLAXIS?
  • Usually yes.
  • Occasionally, in spite of thorough investigation, a cause in not found
  • Idiopathic anaphylaxis
the next slides contain the symptoms that are often associated with anaphylaxis
The next slides contain the symptoms that are often associated with anaphylaxis
  • Usually only some of these symptoms will be experienced
  • The symptoms at the “mild” end of the scale may require no treatment at all
  • The symptoms at the severe end of the scale may become very serious.
mild to moderate
MILD TO MODERATE
  • Tingling or unusual taste in mouth
  • Running nose and eyes, sneezing
  • Itchy skin
  • Hives – red, itchy nettle-rash, urticaria
  • Swelling- puffiness of eyes, lips and limbs. Whole face may appear swollen
moderate to severe
MODERATE TO SEVERE
  • Vomiting
  • Abdominal cramps
  • Uterine cramps
  • Elevation of heart rate
  • Mild wheezing
severe to life threatening
SEVERE TO LIFE-THREATENING
  • Hoarseness or difficulty swallowing due to throat swelling
  • Extreme distress, anxiety, panic, feeling of impending doom
  • Difficulty breathing due to severe asthma or throat swelling
  • Lips turn blue along with “loss of colour”
  • Weakness, dizziness, feeling faint,(drop in BP)
  • Collapse and/or unconsciousness
  • Convulsions
can an anaphylactic reaction be prevented
CAN AN ANAPHYLACTIC REACTION BE PREVENTED?
  • Accurately identify the offending substance
  • Avoid that substance as much as possible
  • Have “rescue medication” available at all times and know when and how to use it
  • Practice using the prescribed “rescue medication” frequently as directed by your doctor
how can the offending substances be accurately identified
How can the offending substances be accurately identified?
  • A detailed medical history
  • Skin tests
  • Blood tests
  • Sometimes, a challenge with the suspect allergen
the limitations of skin tests and blood tests in diagnosing allergy
THE LIMITATIONS OF SKIN TESTS AND BLOOD TESTS IN DIAGNOSING ALLERGY
  • Decision to perform either should be made by doctor who has examined patient and who fully understands the limitation of these tests
  • In anaphylaxis,patient’s skin tests should be performed in the hospital setting
  • Both Skin and blood tests can be difficult to interpret
  • Skin tests should be performed with caution in anaphylaxis patients
the limitations of skin tests and blood tests in diagnosing allergy contd
THE LIMITATIONS OF SKIN TESTS AND BLOOD TESTS IN DIAGNOSING ALLERGY contd.
  • A patient may have a positive skin test or RAST test and be asymptomatic
  • A patient may occasionally have a negative skin test and RAST test to a substance which caused anaphylaxis
  • These tests do not cover all possible antigens
  • Some patients will be positive to every antigen tested
  • Remember that half the population are serologically atopic. What is normality?
slide69

Sometimes no diagnosis can be made immediately, but with patience and the passage of time it becomes apparent

types of skin testing
Types of skin testing
  • Prick tests with commercial antigens
  • Prick tests with fresh antigens
  • Intradermal testing
  • Patch testing for contact urticaria
how can the harmful substances be avoided
How can the harmful substances be avoided?
  • Avoidance depends on the nature of the antigen
  • Will require the use of warning cards, bracelets or necklace, case note tagging
  • Avoidance strategies for bee and wasps can be taught
  • Dissemination information to medical dental staff etc in the case of latex allergy
  • In many cases it is unlikely avoidance will be complete and for life
food avoidance
Food avoidance

A dietitian experienced with anaphylactic patients should always be consulted

WHY?

why dietetic advice
WHY DIETETIC ADVICE?
  • Avoidance in adult usually for life
  • Some foods are difficult (?impossible) to avoid year after year
  • The main risk is when eating out
  • Eliminating some foods from the diet may lead to nutritional deficiency
  • Dietitian experienced in anaphylaxis can give extra advice regarding avoidance strategies
slide81

The dietitian must be experienced in anaphylaxis The approach is different from advising other food allergic patients.

what is rescue medication
WHAT IS RESCUE MEDICATION?
  • “Rescue medication” is prescribed by a doctor for patients who have some risk of an anaphylactic reaction
  • Patients carry it at all times and must be well trained how to use it
  • Rescue medication contains adrenaline and sometime also antihistamines and an asthma inhaler
the decision to prescribe rescue medication
THE DECISION TO PRESCRIBE RESCUE MEDICATION
  • This is often not an easy decision
  • We might be accused of over-prescribing adrenaline
  • Prescribing practices in USA and UK are different and vary within the UK
  • There is no “correct” answer
can the risks of carrying adrenaline or not carrying it outweigh the benefits
CAN THE RISKS OF CARRYING ADRENALINE OR NOT-CARRYING IT OUTWEIGH THE BENEFITS?
  • A death from adrenaline side-effects during an anaphylactic episode would probably be misdiagnosed
  • Many patients carrying adrenaline are not trained in its use
  • To some patients it is a constant reminder of mortality
  • It can sometimes seriously curtail activities
on the other hand
On the other hand……..
  • Most deaths from food induced anaphylaxis occur in patients who received no adrenaline or received too little too late
  • Deaths from anaphylaxis occur in patients who have previously only had a trivial reaction to the antigen in question
slide90

IN SOME PATIENTS ADRENALINE SHOULD BE REGARDED AS “AN INSURANCE POLICY” – IN OTHERS AS A LIFE SAVING MEDICATION

adrenaline prescription a risk assessment
ADRENALINE PRESCRIPTION – A RISK ASSESSMENT
  • The low risk patient
  • The moderate risk patient
  • The high risk patient
moderate risk
MODERATE RISK
  • Most patients carrying adrenaline come into this category
  • They have never been given adrenaline
  • It is likely they will never require to use their rescue medication
  • However a few will and occasionally a patient within this group would die without adrenaline.
  • Like “Clonk-Click”
slide98

Patient should always carry enough adrenaline for two doses. Even then, the first dose may be “wasted”. Three doses?

slide99

If adrenaline is self administered, the patient should always seek medical advice immediately afterwards, even if feeling better

slide100

The indications for using adrenaline are tailored to the individual patient. They may be altered depending on the nature of future reactions

special circumstances
SPECIAL CIRCUMSTANCES
  • Very occasionally, a patient may have experienced a reaction of such severity in the past that a physician that a physician has advised that adrenaline should be given on the least suspicion that an allergy is developing
  • This approach is unusual and means that the patient is considered to be at very high risk of a very severe reaction
above all
ABOVE ALL
  • Remember that fatal reactions to foods are rare and should become rarer still if precautions are taken
  • Make sure the worry of anaphylaxis does not become more incapacitating than the risk