21 - Drug Reactions

Question 1

TIME INTERVAL for FDE, AGEP, Exanthematous Eruption, SJS, TEN, DRESS

Answer 1

FDE: 1st Exposure - 1-2 Weeks, Re-exposure <48 hours.
AGEP < 4 days
Exanthematous Eruption - 4-14 days
SJS,TEN - 7-21 days
DRESS - 15-40 days

Question 2

Selected responsible drugs

Fixed Drug Eruption responsible drugs

Answer 2

TMP-SMX, NSAIDs, Tetracyclines.
Non-pigmenting- Pseudoephedrine

100% of the cases are drug induced!

Question 3

Selected responsible drugs

AGEP Selected responsible drugs

Answer 3

β-Lactam antibiotics, Macrolides
Calcium channel blockers

70% of the cases are drug induced!

Question 4

Selected responsible drugs

DRESS Selected responsible drugs

Answer 4

Anticonvulsants (aromatic)
Lamotrigine (esp. in combination with valproate)
Sulfonamides
Abacavir (HIV treatment)
Allopurinol
Dapsone
Minocycline
Nevirapine

70% to 90% of the cases are drug induced!

Question 5

Selected responsible drugs

Linear IgA bullous
dermatosis

Answer 5

Common- Vancomycin (Unusual variants include TEN-like and morbilliform)
- Less common- Penicillins, Cephalosporins, Captopril> other
ACEi, NSAIDs: diclofenac, naproxen, oxaprozin, piroxicam
- Uncommon- Phenytoin, Sulfonamide antibiotics:
sulfamethoxazole, sulfisoxazole.

הילד עשה פיפי על הקנבס-
פניצילין ופניטואין, קפטופריל,
ACEi
NSAIDs
;ונקומיצין ואנטיביוטיקות

Adults - most of them drug induced. Children- less drug induced

1-15 day after exposure

Question 6

SPECIFIC HLA ALLELES THAT INCREASE THE RISK OF CUTANEOUS DRUG REACTIONS

Allopurinol

Answer 6

B*5801, Asians> European
SJS/TEN, DRESS

Question 7

SPECIFIC HLA ALLELES THAT INCREASE THE RISK OF CUTANEOUS DRUG REACTIONS

Carbamazepine

also known as Tegretol

Answer 7

B*1502- Han Chinese and other Asian populations; SJS/TEN

less risk:
A*3101, hypersensitivity reactions.

Question 8

SPECIFIC HLA ALLELES THAT INCREASE THE RISK OF CUTANEOUS DRUG REACTIONS

Abacavir

Answer 8

B*5701 - DRESS

Question 9

Give an example of Cumulative toxicity of a drug

Answer 9

-MTX can lead to hepatic fibrosis
-Accumulation of minocycline or amiodarone within the skin can lead to cutaneous discoloration.

Question 10

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

Exanthematous eruption (morbiliform drug eruption)

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 10

Child: 10–20%, Adult: 50–70%
Time Interval: 4-14 days
0% Mortality
Drugs:
-ABX-Aminopenicillins, Sulfonamides, Cephalosporins
-Anticonvulsants (aromatic)
-Allopurinol
-HIV treatment- Abacavir, Nevirapine

Question 11

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

Urticaria and Anaphylaxis

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 11

Urticaria<10; Anaphylaxis 30%;
Minutes to Hours
5% mortality in Anaphylaxis
Drugs: Penicillins, Cephalosporins; NSAIDs; Monoclonal antibodies; Radiocontrast

Question 12

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

Fixed drug eruption

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 12

100% drug induced
First exposure: 1–2 weeks; Re-exposure: <48 hours, usually within 24 hours.
0% Mortality
Drugs: TMP-SMX, NSAIDs, Tetracyclines, Pseudoephedrine

Question 13

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

Acute generalized exanthematous pustulosis (AGEP)

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 13

70-90% drug induced
Time interval: <4 days
1-2% Mortality
Drugs: β-Lactam antibiotics, Macrolides. Calcium channel blockers

Question 14

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

Drug reaction with eosinophilia and systemic symptoms (DRESS)/ drug-induced hypersensitivity syndrome (DIHS)

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 14

70-90% drug induced
Time interval (long) - 15-40 days
Mortality- 5-10%
Drugs: Anticonvulsants (aromatic), Lamotrigine (especially in combination with valproate); Sulfonamides; Abacavir; Allopurinol; Dapsone; Minocycline; Nevirapine

Question 15

CHARACTERISTICS OF MAJOR DRUG-INDUCED ERUPTIONS

SJS and TEN

Percentage that are drug-induced, Time Interval, Mortality, Drugs

Answer 15

70-90% drug induced
Time interval: 7-21 days
Mortality: 5% vs 30%
Drugs: Sulfonamides; Anticonvulsants (aromatic); Lamotrigine; Allopurinol; NSAIDs; NNRTIs, e.g. nevirapine

Question 16

Exanthematous Drug Eruptions

Histopathology

Answer 16

Nonspecific findings are typically seen in morbilliform drug eruptions, i.e. a mild superficial perivascular and interstitial lymphocytic infiltrate that may contain eosinophils (up to 70% of cases) in addition to interface changes