Allergy Flashcards
Th2 Response
o Stressed or damaged epithelium will release signalling cytokines
o Cytokines act on Th2, Th9 and ILC2 (Innate Lymphoid Cells T2) - promote the section of IL4, IL5 and IL13
IL-4 stimulates B-cells to produce IgE and IgG4
o These then act on eosinophils and basophils which contribute to tissue injury
Oral vs skin exposure
When an allergen is ingested through the oral route, T-regs (from GI mucosa) inhibit IgE synthesis
Oral tolerance requires induction of CD4+ T-reg cells
T-regs inhibit multiple pro-allergic functions such as inhibiting DC APC function, secretion of IL-10, etc.
Whereas skin and respiratory exposure induces IgE sensitisation
Th2 immune memory responses
o The sensor is the mast cell - allergen causes cross-linking of IgE - histamine, prostaglandins and leukotrienes
o These act on the endothelium increased permeability, smooth muscle contraction and neuronal itch
IgE RAST (radioallergosorbent) blood tests
o (1) Allergen bound to sponge in a plastic cap and patient’s serum is added
o (2) Specific IgE (if present) binds to allergen
o (3) Anti-IgE antibody tagged with a fluorescent label is added
o (4) Amount of IgE/Anti-IgE is measured by fluorescent light signal
Functional allergen tests
• Serial mast cell tryptase
o Tryptase is a pre-formed protein found in mast cell granules
o Peak concentration = 1-2 hours
o Useful if diagnosis of anaphylaxis uncertain (e.g. hypotension/rash in anaesthesia)
• Basophil activation test:
o Measurement of basophil response to allergen IgE cross-linking
o Activated basophils increase expression of CD63, CD203 and CD300 protein
In vivo test: open or blinded allergen challenge
- GOLD STANDARD for food and drug allergy diagnosis
- Increasing volumes of the offending food/drug are ingested
- Take place under close medical supervision
Allergen-specific IgE sensitisation test
o Skin prick and blood tests are used to detect the presence/absence of IgE antibody against external proteins
IMPORTANT: a positive IgE test only demonstrates sensitisation, NOT clinical allergy
80% who have peanut AB are asymptomatic
Concentration – higher levels = more symptoms
Affinity to target – higher affinity = increased risk
Indications of Ice RAST test
o Patients who can’t stop antihistamines (otherwise do skin test)
o Patients with dermatographism
o Patients with extensive eczema
o History of anaphylaxis
o Borderline/equivocal skin prick test results
Diagnosis of anaphylaxis
o Serial measurement of serum tryptase (a highly specific marker for mast cell degranulation)
o Samples taken 1 hour, 3 hours and 24 hours post episode of anaphylaxis
o The rise in tryptase concentration is directly proportional to fall in BP
o DIAGNOSIS = persistent rise in tryptase 24 hours after allergic reaction suggestive of systemic mast cell disease
Management of anaphylaxis
IM ADRENALINE (1 in 1,000)
Adjust body position 100% Oxygen
Fluid replacement Inhaled bronchodilators
Hydrocortisone 100 mg IV (prevent late phase response) Chlorpheniramine 10 mg IV (skin rash)
Reactions that mimic anaphylaxis
o SKIN: Chronic urticaria and angioedema (ACE inhibitors)
o THROAT SWELLING: C1 inhibitor deficiency
o CARDIOVASCULAR: Myocardial infarction and PE
o RESPIRATORY: Very severe asthma, vocal cord dysfunction, inhaled FB
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Investigation for food allergy
o Double-blind oral food challenge = gold standard
o Skin-prick test or specific IgE blood test (useful to confirm a clinical history; useful to exclude allergy)
What each allergy test is useful for
Serial mast cell tryptase- anaphylaxis
Basophil activation- Diagnosis of food and drug allergy
Allergen challenge- Diagnosis of food and drug allergy- gold standard
Skin prick (intradermal)- To exclude allergy (high NPV)
RAST IgE blood test- To exclude allergy (high NPV)
When skin prick is not possible (i.e. cannot take antihistamine)
