Transcript gp allergy 310713

Allergy
Joanna Sheldon
Protein Reference Unit,
St. George’s Hospital
The Investigation of Allergy
ADVERSE REACTION
IMMUNE
INTOLERANCE
TOXIC
PHARMACOLOGIC
EnzymeDefect
Toxin
Biogenic Amines
Biochemical
Microbes
IMMUNE
COMPLEX
CELLULAR
ALLERGY
IgE
PSYCHO SOMATIC
Allergy – a hypersensitivity
reaction






An immune response to something that is not
intrinsically harmful
Need sensitisaton
Re encountering the allergen may elicit and allergic
reaction
Genetic influences
Season of birth
Background infections e.g. parasites
Allergy – a hypersensitivity
reaction
Type I – IgE mediated
Type II – immune complex – antigen membrane bound
Type III – immune complex – antigen “circulating”
Type IV – cell (T) mediated
Allergy – a hypersensitivity
reaction Type I – IgE mediated
Mast cell that has IgE, specific to
an antigen, coated onto its
surface….cell is primed and able
to respond
Encounter with the antigen
(components of a banana) cross links
the IgE on the mast cell surface.
Signal within the cell causes
granules or vesicles of
inflammatory mediators to go
to the mast cell surface and
release their contents.
RAPID immediate to ~ 20 mins
Mast cell – contains
many granules of
potent inflammatory
mediators
Mediators cause increase vascular
permeability, smooth muscle
contraction, mucous secretion etc.
and activate complement - can be
local or systemic
Allergy – a hypersensitivity
reaction
Subject “sensitised”
 Make IgE antibodies
 IgE binds to IgE receptor on mast cells
 Re-encounter antigen
 Cross linking of IgE caused
degranulation of mast cell
 Release of mediators

HYPERSENSIVITY REACTIONS:
EXAGGERATED INAPPROPRIATE REACTIONS TO
NORMALLY HARMLESS AGENTS
HISTAMINE
vasodilation, #Vasc. Permeability, smooth muscle contraction
PROTEASES
digest basement membrane, #vasc. Perm, cleave of C3 C3a
PROTEOGLYCANS heparin – anticoagulant activity
CHEMOTACTIC FACTORS recruit neutrophils + eosinophils
PLATELET ACTIVATING FACTOR vasodilation (powerful)
PROSTAGLANDINS
# vasc perm; bronchoconstrictors, vasodilation
Plus Tryptase, Eosinophil cationic protein, Bradykinin etc.
SYMPTOMS
Headache, runny nose, sneezing, itching, abdo pain,
dermatitis, asthma, vomiting, diarrhoea, anaphylaxis,
malabsorption, eczema, rash, conjunctivitis, dermatitis
MILD – INCONVENIENT
DAMAGING TO HEALTH POTENTIALLY FATAL
1
2
3
4
5
Sensitisation
Re-challenge
Cell
Degranulation
Mediator
Release
Symptoms
Pollen is an Antigen
Re-challenge by the antigen
e.g. further exposure to pollen,
causes degranulation and the
release of mediators such as
histamines, prostaglandins
& leucotienes.
Antigens are
presented to the T cells
of the immune system
by the Antigen
Presenting Cells
Pollen
B
Cell
Antigen
Presenting
Cell
Mediators cause
inflammation and
other symptoms
associated with
allergic reactions
Skin
• Red and itchy
• Swollen eyes
Lungs
• Asthma
• Bronchial
constriction
Chemical
messengers
e.g.
Airway
• Sneezing
• Runny Nose
Histamines
T
Cell
T cells produce
cytokines which
stimulate B cells
to produce IgE
Sensitised
blood or
tissue cell
IgE sticks to the surface
of Mast cells and other
cells in the blood and
surrounding tissues
Prostaglandins
PAE
GI tract
• diarrhoea
• Vomiting
• Abdo pain
DRUG
INTERVENTION
Allergy diagnosis




HISTORY
EXAMINATION
SKIN TESTING
TOTAL AND SPECIFIC IgE
Allergy diagnosis - history
What
Asthma
Nasal polyps
Angioedema
type of symptoms
Bronchitis
Catarrah
Abdominal pain
Diarrhoea
Headache/Migraine Arthralgia
How severe
Mild and inconvenient
When
Hay fever
Urticaria
Nettle rash
Life threatening
do the sysmptoms occur?
All year round
Jan, Feb, Mar, Apr, May, Jun, Jul, Aug, Sep, Oct, Nov, Dec
Why ask about the time ot the year?
Pollen Calendar
Allergy diagnosis - history
When
are the symptoms most frequent?
Out doors
Day time
At home
In doors
Night time At work/school
What
On waking
Other
pets do you have?
Has
the patient ever had a severe reaction (e.g.
anaphylaxis) to the suggested allergen/allergens?
Is
there a family history of allergy?
Is
the patient on any treatment? (give brief details)
Has
the patient kept (or is keeping) and allergy diary?
Date and time, What were they doing or eating, Symptoms –
type and severity
Allergy diagnosis - examination
general
examination
lung function tests –
Particularly for respiratory allergens
check
skin
? weight loss
Particularly for food allergens
Allergy diagnosis – skin testing
immediate
reaction
easy to do in clinic
Assess how the patient reacts
can be risky – must be done with resuscitation facilities
Impossible if patient has skin symptoms
Impossible if patient on antihistamine
Can lack sensitivity for food allergens
Difficult with some “toxic” or insoluble antigens
Allergy diagnosis – IgE and
specific IgE
slower
expensive
measures
the IgE that is not bound to mast cells – the
“overflow”
can give false positives with high total IgE
O.K. in patients with skin symptoms and on anti
histamine
O.K. with toxic allergens
not dangerous
Allergy diagnosis – reasons to
investigate
Allergen
difficult to exclude
Common food
Favourite pet
Severe
(or worsening) reaction
Identifying the allergen so the patient can carefully
and diligently exclude it
Result
will alter management
Desensitisation
Self injecting adrenaline
Allergy diagnosis – how to
investigate
Identify
potential allergens from history and
examination ± allergy diary
If the allergen is obvious and easy to exclude – no
testing needed e.g. tree pollen or mango allergy
Combination of skin testing and total and specific IgE
Good H and E should identify <5 allergens to test –
more can give false positives and be misleading
Specific IgE
We keep over 100 allergens “in stock”
Common foods: egg, milk, fish, peanut, soya, wheat
“serious foods”: shell fish, nuts
“silly foods”: broccoli, sprouts, mango, reindeer
Common inhaled: mixed grass, trees, weeds, cat,
dog, house dust mite, feathers
Common animals: cat, dog, horse, rodents
Miscellaneous: penicillin
Specific IgE
 We run them every week
Grade
0
1
2
3
4
5
6
KU/L
<0.35
0.35 – 0.7
0.7 – 3.5
3.5 – 17.5
17.5 – 50
50 – 100
>100
Interpretation
NEG
WEAK POSITIVE
POSITIVE
STRONG POSITIVE
Cross
reactivities
Favourite allergy requests












Apricots and andrex toilet paper
Gary Linekar crisps (cheese and onion)
Every allergen you have
Mussels, scallops, oysters, clams ……aged 28 months!
Chilli Vodka, Bacardi Breezer (Cranberry), Red Bull
Toffee vodka
Exotic fruit salad (and Cream)
Dates, prunes, figs ……..symptoms diarrhoea
General allergy test
Cheap perfume
Mulberry pollen
Mixed pollens …..so the council could send them to
Switzerland to live in the mountains