Immunity 3 Drug Allergy

Question 1

Define the term ‘drug hypersensitivity reaction’ (DHR)

Answer 1

Type B drug reactions - unpredicatable

Question 2

What is Type A reaction and give an example?

Answer 2

Type A

• Related to Pharmacology of drug
• Predictable
• Usually dose-dependent
• High morbidity, Low mortality

Eg
Drowsiness with first-generation anti-histamines
Liver failure in paracetamol overdose
Nausea and constipation with opiates
Dry mouth with tricyclic anti-depressants

Question 3

What is Type B reaction and give an example?

Answer 3

Type B

• Not (directly) related to the pharmacology
• Unpredictable
• (Often) dose-independent
• High mortality

Question 4

Describe the immediate DHR reaction (i.e what happens during mast cell activation)?

Answer 4

• Within 1 hour
• Skin: urticaria, angioedema
• Respiratory: rhinitis, bronchospasm, laryngeal oedema
• Gut: vomiting, diarrhoea (very rare)
• Cardiovascular collapse
• Generally the result of mast cell activation

*** IgE-mediated, or a form of non-allergic immediate DHR

Question 5

What are non-igE mediated reactions?

Answer 5

• Non- specific mast cell activation
  
  • ACEI- raised levels of bradykinin
  • Non- specific mast cell activation (opiates)
• NSAIDS- frequently causes urticaria, anaphylaxis

Question 6

What are the key features of an immediate DHR?

Answer 6

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

Question 7

What can you measure to confirm acute anaphylaxis?

Answer 7

Serum tryptase levels

released from mast cells

Question 8

How can non-immediate DHR reactions be further classified?

Answer 8

Delayed
e.g. : delayed urticaria, maculo-papular eruptions, fixed drug eruptions

Systemic

e.g. TEN, SJS, DRESS, vasculitis

Question 9

What are the key features of non-immediate DHR?

Answer 9

• Not directly related to a drug dose, although may appear to be so by chance
• Typically during treatment course
• Antimicrobials=biggest group

Question 10

Describe the features of SJS/TENS?

Answer 10

the dangerous non-immediate DHR

Fever, cough, conjunctivitis, mucosits

high mortality

Question 11

What are the features of standard type IV hypersensitivity?

Answer 11

Onset 3-8 days into course

Maculo-papular

Skin may be dry/ inflamed

Gradually fades over days and weeks

No systemic upset

Question 12

What is the mechanism that underlies IgE mediated allergy?

Answer 12

• IgE binds its specific allergen
• Cross-linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
• The intracellular portion of the receptor becomes phosphorylated
• The resulting intracellular cascade leads to cellular activation
• Mast cell ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators

Question 13

Outline the acute management of immediate

Answer 13

1. ABCD
2. IM adrenaline
3. IV fluid challenge

Question 14

What do results from Beta Lactam allergy testing tell you and how do you confirm?

Answer 14

Negative results- high NPV- confirm with brief challenge test

Positive- Perform challenge with alternative to demonstrate tolerance