Immunity 3) Drug allergy Flashcards
What percentage of the UK population report a penicillin allergy?
10%
How many UK hospital admissions are caused by drug hypersensitivities per year?
≥50,000
What are the 2 types of adverse drug reactions?
Type A
Type B
What is a type A adverse drug reaction?
Related to pharmacology of drug
Predictable
Usually dose-dependent
High morbidity, low mortality
What are examples of type A adverse drug reactions?
Drowsiness with 1st class antihistamines Liver failure in paracetamol overdose Nausea and constipation with opiates Dry mouth with tricyclic antidepressants
What is a type B adverse drug reaction?
Not directly related to pharmacology Unpredictable Often dose-independent High mortality Anything that clinically resembles an allergic or immunological reaction
When does an immediate drug hypersensitivity reaction occur?
Within 1h of last dose
What symptoms occur with an immediate DHR?
Skin: urticaria, angioedmea
Resp: rhinitis, bronchospasm, laryngeal oedema
Gut: vomiting, diarrhoea
Cardiovascular collapse
Why does an immediate DHR occur?
Mast cell activation
What can cause a non-IgE mediated DHR?
Opiates Myorelaxants Radiocontrast media ACEi NSAIDs
Describe the steps of an IgE mediated DHR
IgE binds its specific allergen
Cross-linking IgE antibodies by allergen
Clustering of FcεR1 receptors
Intracellular portion of receptor becomes phosphorylated
Intracellular cascade leading to cellular activation
Mast cell degranulation releasing histamine, tryptase and other pre-formed mediators
What are the key features of immediate DHR?
Within 1 hour last dose
Soon after initiation - usually 1st dose
Appropriate clinical features of mast cell degranulation
Recede rapidly after drug is stopped
Why are serum tryptase levels measured?
Levels recommended to confirm acute anaphylaxis
Tryptase release from mast cells during anaphylaxis
What is the allergist approach to immediate DHR?
Often no diagnostic tests other than drug provocation (challenge test)
Pragmatic approach vs definitive approach
Why is B lactam allergy over-reported?
Sensitisation lost at a rate of 10% per year but label persists
Rash may have been an infection rather than drug related
Different drug caused the rash
What drugs can cause a B lactam allergy?
Includes multiple different antibiotic groups Penicillins - natural G and V Penicillinase - resistant (flucloxacillin) Aminopenicillins Extended-spectrum Cephalosporins Carbapenems Monobactams
What alternative to penicillin can be used?
Non-B lactams
Cross-reactivity with 2/3rd generation cephalosporins is very low
Describe the delayed non-immediate DHR symptoms
Delayed urticaria
Maculo-papular eruptions
Fixed drug eruptions
Describe the systemic non-immediate DHR symptoms
TEN - toxic epidermal necrolysis
SJS
DRESS - drug reaction with eosinophilia and systemic symptoms
Vasculitis
What are the key features of a non-immediate DHR?
Not directly related to a drug dose
Typically during treatment course
Clinical features not in keeping with mast cell degranulation
Continue for some time after drug is stopped
Antimicrobials are commonest
What are the symptoms of SJS / TENS?
Fever
Cough
Conjunctivitis
Mucositis
Describe a standard type IV hypersensitivity
Onset 3-8 days into course Maculo-papular Skin may be dry / inflamed Gradually fades over days and weeks No systemic upset
What questions should be taken for an allergy reaction?
When
Which drug
Nature of symptoms
When did it happen during the course
Time between last dose and symptoms
How long did it last once the drug was stopped
Has drugs or alternatives subsequently been tolerated
When is a referral to immunology needed?
Drug will be needed again
Choice restricted
Cross-reactivity questions
Diagnostic doubt
When is a referral to immunology not needed?
Drug unlikely to be needed again
Minor reaction e.g. macula-papular rash
Alternatives readily available
Nothing more to add
What reactions can NSAIDs produce?
Cutaneous only - urticaria / angioedema
True anaphylaxis
Aspirin-sensitivity asthma / rhinitis
