lecture 27

Question 1

Define drug-induced hypersensitivity.

Answer 1

A low frequency serious adverse drug reactions with an immunological etiology to an otherwise safe and effective therapeutic agent

Question 2

State the 4 key characteristics of DIHR.

Answer 2

Rare
Unpredictable
Complex
Potentially fatal

Question 3

Distinguish between the two types of DIHR.

Answer 3

Immediate: occur within 1 hour, type I, IgE-mediated
- only occurs after prior exposure to the antigen or similar antigen

Delayed: occurs >1 hour, type IV or III, T cell-mediated
- sensitization may occur through prior exposure or repeated dosing

Question 4

State the two primary reasons most people who claim to have an allergy to penicillin actually tolerate the drug.

Answer 4

10% of the population claim to have a PCN allergy. ~90% of those can actually tolerate the drug.

1. 50% of people with IgE-mediated PCN allergy lose sensitivity within 5 years; >80% within 10 years.
2. In some patients, the rash is caused by concurrent viral infection.

Question 5

State the two phases of delayed hypersensitivity reactions.

Answer 5

Sensitization Phase: type IV DTH, initial exposure to the antigen

Effector Phase: hapten/antigen re-exposure

Question 6

Identify the most common organ effected by delayed hypersensitivity reactions.

Answer 6

Skin:
- prior viral exposure may prime the immune system for DIHR and explain why skin is uniquely targeted
- 10-30% of ADR involve the skin
- ~90% of drug eruptions are benign
- serious cutaneous adverse reactions (SCAR) occur at low frequency (~1 per 1 million patients exposed)
- some reactions involve other organs, such as the liver

Question 7

State the time frame at which most drug eruptions occur.

Answer 7

Exanthema (~90%): onset 4-14 days after start of therapy, last ~1 week

Erythema Multiforme, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN): onset 1-3 weeks after start of therapy

Question 8

Describe how DRESS is differentiated from other DIHR.

Answer 8

Drug Reaction with Eosinophilia and Systemic Symptoms
- characterized by fever, skin rash, lymphadenopathy, hematological abnormalities, and internal organ involvement
- 10% mortality
- onset 2-8 weeks after start of therapy
- anticonvulsants, antibiotics, and allopurinol