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
What are the symptoms of severe exanthematous drug eruption
High fever
Involvement of mucous membranes
Widespread oedema and erythema
Blisters / necrosis
Skin pain
Dyspnea
Which type of hypersensitivity causes urticarial drug eruptions
Type 1
Urticarial drug eruptions can occur on first exposure as well. Why
Due to pseudo-allergic reaction which is not dependent on the immune system (not IgE dependent)
What is pseudo allergic reaction
When it causes direct release of histamine and cytokines from mast cells without needing IgE to bind to Fc receptors of mast cells first
Onset of symptoms in urticarial drug eruptions due to type 1 hypersensitivity
Immediate reaction
Drugs that causes urticarial reaction due to type 1 hypersensitivity
Beta lactam antibiotics
Carbamezapine, phenytoin (anti-epileptics
Examples of beta lactam antibiotics
Penicillins - amoxicillin, penicillin
Cephalosporin - cephalexin, ceftriazone
Drugs that can cause urticarial reaction due to pseudo allergic reaction
Opiates
NSAID
Aspirin
Vancomycin
Symptoms of urticarial drug eruptions
Pruritic red hives rash
Angio-oedema
What are the subtypes of bullous / pustular drug eruptions
Acneiform
Acute generalised exanthematous pustulosis
Drug induced bullous pemphigoid
Linear IgA disease
What is Acneiform
Pus filled, red, acne like bumps but are not acne
How to differentiate between acneiform drug eruption and acne
Acneiform resolves with discontinuation of drug
Acneiform has an acute onset
Drugs that causes aceniform eruption
Steroids
Androgens
Lithium
Isoniazid
What is isoniazid used for
treat TB
Onset of symptoms for acute generalised exanthematous pustulosis is
within 2 days of exposure
Drugs that causes acute generalised exanthematous pustulosis
Beta lactam antibiotics
CCB
Tetracyclines
Hydroxycloroquine
Carbamazepine
Paracetamol
What is hydroxycloroquine used for
It is a DMARD, used for rheumatoid arthritis
It is also used to treat malaria
Symptoms of acute generalised exanthematous pustulosis
Widespread rash
Many small, non-follicular, sterile pustules
What are non-follicular pustules
The inflammatory infiltrate does not accumulate in hair follicles
What is a sterile pustule
Bacterial culture obtained from the pustular fluids is negative
Symptoms of drug induced bullous pemphigoid
Itchy large bullae
Eruptions of bullae causes crusted erosions
Drugs that causes drug induced bullous pemphigoid
PD1 inhibitor immunotherapies
ACEi
Penicillin
Furosemide
DPP4
What is linear IgA disease
Linear deposits of IgA at basement membrane causing bullae
Which drug can trigger linear IgA disease
Vancomycin
What is fixed drug eruption
Reaction that recurs at the same site on re-exposure to the medication
Which type of hypersensitivity causes fixed drug eruption
Type 4
What drugs causes fixed drug eruption
NSAID
Paracetamol
Tetracycline
Sulfonamides
Type of rash caused by fixed drug eruption
Well demarcated round plaques
Red
Painful
Persistent pigmentation even after stopping the drug
May occur as bullous / on mucous membranes
Which mucous membranes can be affected by fixed drug eruption
Lips
Tongue
Genitals
What is Stevens-Johnson Syndrome (SJS)
Dermatological emergency most commonly caused by severe drug reactions but can also be caused by viral infections
What is Toxic epidermal necrolysis
The most severe form of Stevens-Johnson Syndrome
Drugs that can cause SJS
Sulfonamides
Beta lactam antibiotics
NSAID
Anti-epileptics - carbamezapine and phenytoin
Allopurinol
Viral infections that can cause SJS
Herpes Simplex
EBV
HIV
Influenza
Hepatitis
When do symptoms of SJS usually present
within a week of taking a medication
Symptoms of SJS
Mucosal ulceration of at least 2 mucosal membranes
Erythematous macules that become target shaped
Flaccid blisters
Systemically unwell
What are the mucosal membranes that can be affected by SJS
Mouth
Conjunctiva
Urethra
Pharynx
GI tract
What is a target lesion
Round lesion with 3 colour zones:
- darker center
- raised pale pink ring around the center
- bright red outermost ring
Investigations for SJS
Nikolsky sign
Skin biopsy
What is Nikolsky sign
When slightly rubbing the roof of the lesion using eraser part of the pencil causes the lesion to open
How does SJS lead to death
Due to damage to the skin barrier = the skin loses its function
- dehydration
- infection
- hypothermia
- disseminated intravascular coagulation
What is disseminated intravascular coagulation
Coagulation pathway becomes overreactive causing formation of blood clots
Management of SJS
Supportive - pain relief, antibiotics if there is infection
Ophthalmology referral
What is drug phototoxicity
Non-immunological skin reaction due to light activation of a photo-reactive drug
Which UV light most commonly causes drug phototoxicity
UVA
Common phototoxic drugs
NSAID
CCB
Thiazide diuretics
Amiodarone
Tetracycline
Quinine
Chlorpromazine
What is quinine used for
Malaria
Leg cramps
What is chlorpromazine used for
Psychosis, anxiety, mania
What are the skin reactions due to phototoxicity
Exaggerated sunburn
Pseudoporphyria
Exposed telangiectasia
Delayed erythema and pigmentation
Immediate prickling with delayed erythema and pigmentation
What is psuedoporphyria
Bullous photodermatosis with features of porphyria cutanea tarda but without any abnormalities in porphyrin metabolism
What is porphyrin cutanea tarda
Painful blisters that develop when you become exposed to the sun
What causes porphyrin cutanea tarda
Deficiency in UROD enzyme (uroporphyrinogen decarboxylase) which is needed to break down porphyrin.
Build up of porphyrin causes porphyrin to absorb sunlight and become activated and causes damage to skin
Which drugs cause exaggerated sunburn due to phototoxicity
Thiazides
Quinine
Tetracycline
Which drug causes pseudoporphyria due to phototoxicity
NSAID
Which drug causes telangiectasia on sun exposed sites due to phototoxicity
CCB
Which drugs cause delayed erythema and pigmentation due to phototoxicity
Psoralen
When is psoralen used
PUVA (phototherapy) for psoriasis
Which drug causes immediate prickling with delayed erythema and pigmentation due to phototoxicity
Amiodarone
Chlorpromazine
Management of phototoxicity
Discontinue the drug and use alternative
Topical steroids
