Week 1.5 Flashcards
What are the 2 stages in all hypersensitivity reactions
Sensitisation stage
Effector stage
Features of type 1 hypersensitivity reaction
Immediate reaction - symptoms onset minutes up to Hours
IgE mediated
Mechanism of type 1 hypersensitivity reaction
- On first exposure to allergen, B cells produce IgE antibodies
- Some remaining IgE antibodies bind to Fc receptors of mast cells
- Mast cells circulate the blood stream
- On re-exposure to the allergen, the antigen binds onto IgE on mast cells causing mast cells to degranulate
- Mast cells release histamine and inflammatory cytokines
Common allergens causing type 1 hypersensitivity
Pollen
Food
Animals
Drugs
Symptoms that can be caused by type 1 hypersensitivity
Urticaria - very itchy lesions that look like hives
Angioedema
Anaphylaxis (if severe reaction)
Asthma
Symptoms of anaphylaxis
Laryngeal / pharyngeal oedema
Bronchospasm
tachypnea
Hypotension
Tachycardia
Urticaria
Allergic rhinitis / conjunctivitis
Investigations for type 1 hypersensitivity
History
Skin prick test
Challenge test if skin prick test is negative but history strongly suggests so
First line treatment for type 1 hypersensitivity
Avoid allergen
Management for acute T1 hypersensitivity attack
- Anti-histamines
- Corticosteroids
- Epi pen (adrenaline pen) if anaphylaxis
Examples of anti-histamines
Chlorphenamine
Diphenhydramine
Examples of corticosteroids used in type 1 hypersensitivity
Prednisolone
Features of type 2 hypersensitivity
Takes hours - days for reaction after exposure
IgG and IgM mediated
Cytotoxic reaction
How does IgG and IgM cause cytotoxic reaction in type 2 hypersensitivity
Activation of complement system
Antibody dependent cell mediated cytotoxicity (ADCC)
Opsonization
Describe the antibody-dependent cell mediated cytotoxicity in type 2 hypersensitivity
- IgG/IgM binds to antigens
2 Natural killer cells bind to the Fc portion of IgM/IgG antigen complexes - NK cells causes cell death
Examples of conditions due to Type 2 hypersensitivity
Haemolytic anaemia
Goodpasture’s syndrome
Grave’s disease
Bullous pemphigoid
What is Goodpasture’s syndrome
When the IgG and IgM antibodies are directed to attack a specific collagen found in basement membrane of alveoli and glomeruli
Causes lungs and kidney damage
Presentation of Goodpasture’s syndrome
Haemoptysis
SOB
Renal dysfunction - decreased urine output
Renal failure
Features of type 3 hypersensitivity
Takes hours - days for reaction to occur after exposure
Antigen-antibody immune complex mediated
Difference between type 2 and type 3 hypersensitivity
In type 3, the antibodies are bound to soluble antigens unlike in type 2 where IgG and IgM are bound to antigens on cells
In type 3, it triggers inflammation cascade in certain areas instead of cytotoxicity in type 2
Mechanism of type 3 hypersensitivity
- sensitisation
- effector stage: Antibody covers the soluble antigen forming antibody-antigen complexes. The complexes can move and deposit in certain areas and trigger inflammation there
The immune complexes in type 3 hypersensitivity often deposit in
Blood vessels
Synovial joints
Glomerular basement membrane
Examples of conditions due to type 3 hypersensitivity
Rheumatoid arthritis
SLE
Post streptococcal glomerulonephritis
Features of type 4 hypersensitivity
Takes days for reaction to occur after exposure
T cell mediated
Why is type 4 hypersensitivity called delayed hypersensitivity
Because it takes time for T cells to recruit to sites where antigen is at hence causes delayed response
Examples of conditions due to type 4 hypersensitivity
Contact dermatitis
Drug eruptions - exanthematous and fixed drug eruptions
What are drug eruptions
Symmetrical skin eruption due to certain medications and this skin eruption resolves after withdrawal of the medication
The amount of time drug eruptions take to resolve depends on
the half life of the drug
Different types of drug eruptions (depending on presentation)
Exanthematous drug eruption
Urticarial drug eruption
Bullous or pustular drug eruption
Fixed drug eruption
Risk factors for drug eruptions
Elderly, young adults
Females
Genetics
HIV / EBV / CMV / cystic fibrosis
Drugs that have higher risk of causing drug eruptions
What are the drugs that have higher risk of causing drug eruptions
Beta lactam antibiotics
NSAID
Anti-epilepsy drugs
Topical drugs
Which type of drug eruption is the most common
Exanthematous drug eruption
Exanthematous drug eruption is due to which type of hypersensitivity
Type 4
Onset of symptoms of exanthematous drug eruptions
4 - 21 days
May appear within 1-3 days on re-exposure to the drug
What are the drugs that commonly causes exanthematous drug eruption
Penicillin (beta lactam antibiotics)
Carbamezapine and phenytoin
Allopurinol
Erythromycin
Streptomycin
NSAID
What type of drugs are carbamezapine and phenytoin
Anti-epileptic drugs
What is allopurinol used for
To treat gout attacks
Symptoms of mild - moderate exanthematous drug eruption
Widespread bilateral symmetrical macules and papule
Pruritus
Mild fever
Which parts of the body is often spared in exathematous drug eruption
Mucous membranes
Axilla
groin
hands
feet