Allergy

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Allergy

• Joanna Sheldon
• Protein Reference Unit,
• St. Georges Hospital

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The Investigation of Allergy

• ADVERSE REACTION
• IMMUNE INTOLERANCE TOXIC PSYCHO SOMATIC
  PHARMACOLOGIC
• EnzymeDefect Toxin
• Biogenic Amines Biochemical
• Microbes
• ALLERGY
• IgE IMMUNE CELLULAR
• COMPLEX

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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

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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

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Allergy a hypersensitivity reaction Type I
IgE mediated
Encounter with the antigen (components of a
banana) cross links the IgE on the mast cell
surface.
Mast cell that has IgE, specific to an antigen,
coated onto its surface.cell is primed and able
to respond
Y
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
Y
Y
Y
Y
Y
Y
Mediators cause increase vascular permeability,
smooth muscle contraction, mucous secretion etc.
and activate complement - can be local or
systemic
Mast cell contains many granules of potent
inflammatory mediators
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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

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HYPERSENSIVITY REACTIONSEXAGGERATED
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
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Sensitisation
Re-challenge
Cell Degranulation
Mediator Release
Symptoms

• Skin
• Red and itchy
• Swollen eyes

Pollen is an Antigen Antigens are presented to
the T cells of the immune system by the Antigen
Presenting Cells
Re-challenge by the antigen e.g. further exposure
to pollen, causes degranulation and the release
of mediators such as histamines, prostaglandins
leucotienes.
Mediators cause inflammation and other symptoms
associated with allergic reactions

• Lungs
• Asthma
• Bronchial constriction

Pollen
B Cell
Antigen Presenting Cell
Chemical messengers e.g. Histamines Prostaglandin
s PAE
INFLAMMATION

• Airway
• Sneezing
• Runny Nose

Chemical messengers cytokines
IgE
T Cell
Sensitised blood or tissue cell
INFLAMMATION

• GI tract
• diarrhoea
• Vomiting
• Abdo pain

T cells produce cytokines which
stimulate B cells to produce
IgE
IgE sticks to the surface of Mast cells and other
cells in the blood and surrounding tissues
DRUG INTERVENTION
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Allergy diagnosis

• HISTORY
• EXAMINATION
• SKIN TESTING
• TOTAL AND SPECIFIC IgE

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Allergy diagnosis - history

• What type of symptoms
• Asthma Bronchitis Catarrah Hay fever
  
• Nasal polyps Abdominal pain Diarrhoea
  Urticaria
• Angioedema Headache/Migraine Arthralgia
  Nettle rash
• How severe
• Mild and inconvenient Life threatening
• When do the sysmptoms occur?
• All year round
• Jan, Feb, Mar, Apr, May, Jun, Jul, Aug, Sep, Oct,
  Nov, Dec

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Why ask about the time ot the year? Pollen
Calendar
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Allergy diagnosis - history

• When are the symptoms most frequent?
• Out doors Day time At home On
  waking
• In doors Night time At work/school
  Other
• What 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

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Allergy diagnosis - examination

• general examination
• lung function tests
• Particularly for respiratory allergens
• check skin
• ? weight loss
• Particularly for food allergens

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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

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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

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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

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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 lt5 allergens to test
  more can give false positives and be misleading

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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

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Specific IgE

• We run them every week
• Grade KU/L Interpretation
• 0 lt0.35 NEG
• 1 0.35 0.7 WEAK POSITIVE
• 2 0.7 3.5
• 3 3.5 17.5 POSITIVE
• 4 17.5 50
• 5 50 100 STRONG POSITIVE
• 6 gt100

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Cross reactivities
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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