Immunity 3) Drug allergy

Question 1

What percentage of the UK population report a penicillin allergy?

Answer 1

10%

Question 2

How many UK hospital admissions are caused by drug hypersensitivities per year?

Answer 2

≥50,000

Question 3

What are the 2 types of adverse drug reactions?

Answer 3

Type A

Type B

Question 4

What is a type A adverse drug reaction?

Answer 4

Related to pharmacology of drug
Predictable
Usually dose-dependent
High morbidity, low mortality

Question 5

What are examples of type A adverse drug reactions?

Answer 5

Drowsiness with 1st class antihistamines
Liver failure in paracetamol overdose
Nausea and constipation with opiates
Dry mouth with tricyclic antidepressants

Question 6

What is a type B adverse drug reaction?

Answer 6

Not directly related to pharmacology
Unpredictable
Often dose-independent 
High mortality
Anything that clinically resembles an allergic or immunological reaction

Question 7

When does an immediate drug hypersensitivity reaction occur?

Answer 7

Within 1h of last dose

Question 8

What symptoms occur with an immediate DHR?

Answer 8

Skin: urticaria, angioedmea
Resp: rhinitis, bronchospasm, laryngeal oedema
Gut: vomiting, diarrhoea
Cardiovascular collapse

Question 9

Why does an immediate DHR occur?

Answer 9

Mast cell activation

Question 10

What can cause a non-IgE mediated DHR?

Answer 10

Opiates
Myorelaxants
Radiocontrast media
ACEi
NSAIDs

Question 11

Describe the steps of an IgE mediated DHR

Answer 11

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

Question 12

What are the key features of immediate DHR?

Answer 12

Within 1 hour last dose
Soon after initiation - usually 1st dose
Appropriate clinical features of mast cell degranulation
Recede rapidly after drug is stopped

Question 13

Why are serum tryptase levels measured?

Answer 13

Levels recommended to confirm acute anaphylaxis

Tryptase release from mast cells during anaphylaxis

Question 14

What is the allergist approach to immediate DHR?

Answer 14

Often no diagnostic tests other than drug provocation (challenge test)
Pragmatic approach vs definitive approach

Question 15

Why is B lactam allergy over-reported?

Answer 15

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

Question 16

What drugs can cause a B lactam allergy?

Answer 16

Includes multiple different antibiotic groups
Penicillins - natural G and V
Penicillinase - resistant (flucloxacillin)
Aminopenicillins
Extended-spectrum
Cephalosporins
Carbapenems
Monobactams

Question 17

What alternative to penicillin can be used?

Answer 17

Non-B lactams

Cross-reactivity with 2/3rd generation cephalosporins is very low

Question 18

Describe the delayed non-immediate DHR symptoms

Answer 18

Delayed urticaria
Maculo-papular eruptions
Fixed drug eruptions

Question 19

Describe the systemic non-immediate DHR symptoms

Answer 19

TEN - toxic epidermal necrolysis
SJS
DRESS - drug reaction with eosinophilia and systemic symptoms
Vasculitis

Question 20

What are the key features of a non-immediate DHR?

Answer 20

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

Question 21

What are the symptoms of SJS / TENS?

Answer 21

Fever
Cough
Conjunctivitis
Mucositis

Question 22

Describe a standard type IV hypersensitivity

Answer 22

Onset 3-8 days into course
Maculo-papular
Skin may be dry / inflamed
Gradually fades over days and weeks
No systemic upset

Question 23

What questions should be taken for an allergy reaction?

Answer 23

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

Question 24

When is a referral to immunology needed?

Answer 24

Drug will be needed again
Choice restricted
Cross-reactivity questions
Diagnostic doubt

Question 25

When is a referral to immunology not needed?

Answer 25

Drug unlikely to be needed again
Minor reaction e.g. macula-papular rash
Alternatives readily available
Nothing more to add

Question 26

What reactions can NSAIDs produce?

Answer 26

Cutaneous only - urticaria / angioedema
True anaphylaxis
Aspirin-sensitivity asthma / rhinitis