Serious Adverse Cutaneous Reactions to Drugs

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Serious Adverse Cutaneous Reactions to Drugs

• Michael Bigby, MD
• Department of Dermatology
• Harvard Medical School and
• Beth Israel Deaconess Medical School
• Boston, MA
• mbigby_at_bidmc.harvard.edu

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Identifying Drug Eruptions

• Identify rash as a drug eruption
• Exclude alternative causes
• Examine exposure-rash interval
• Note response to drug withdrawal
• Check drugs history
• Note response to re-exposure

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Common Drug Rashes

• Exanthem
• Urticaria
• Fixed-drug eruption

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Identifying Culprit Drug

• Timing
• Rates of reactions
• Response to withdrawal
• Re-challenge

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Timing

• 1 to 3 days
• Up to 2 weeks (antibiotics and allopurinol)

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Determining Rates of Reactions

• Prospectively collected data
• Retrospective studies
• Spontaneous reports/consumption

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Common Urticaria Producers

• Same as exanthem producers
• Histamine releasers

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Common Fixed-drug Producers

• Co-trimoxazole
• Naproxen
• Dipyrone
• Oxicams
• Tetracyclines
• Phenolphthalein

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Serious Drug Rashes

• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Drug hypersensitivity syndrome

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Toxic Epidermal Necrolysis

• Prodrome fever, malaise
• Pupuric plaques, bullae, face torso
• Mucosa involved
• Wide areas of epidermal detachment gt30
• Mortality 30 (infection, respiratory)

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Epidemiology of TEN

• Incidence 0.4 to 1.2 per million person-years
• Drug-induced (95)
• High incidence with some drugs (1 to 14 per
  100,000 users)

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Epidemiology of TEN

• Sulfonamides
• Trimethoprim-sulfamethoxazole
• Carbamazepine
• Oxicams
• Excess risk per million users/week
• NEJM 19953331600

4.5 4.3 2.5 2.0
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Toxic Epidermal Necrolysis

• Hydantoins
• Sulfonamides
• NSAIDS
• Allopurinol

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Stevens-Johnson Syndrome

• Prodrome fever, malaise
• Pupuric plaques, bullae, face torso
• Mucosa involved
• Limited area of epidermal detachment lt10
• Mortality lt5

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Epidemiology of SJS

• Incidence and 1.2 to 6 per million person-years
• Drug-induced (50)
• High incidence with some drugs

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Drugs Implicated in TEN and SJS

• Hydantoins
• Sulfonamides
• NSAIDS
• Allopurinol

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Drug Hypersensitivity Syndrome

• Exanthem
• Fever
• Hepatitis
• Lymphadenopathy

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Drugs Implicated in Hypersensitivity

• Hydantoins
• Anti-epileptics
• Sulfonamides

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NEJM 19943311272
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NEJM 19943311272
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Mimics of Drug Rashes

• Erythema Multiforme
• Grovers disease
• Pityriasis rosea
• Viral exanthem
• Graft vs host disease

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Mimics of Drug Rashes

• Grovers disease
• Pityriasis rosea
• Viral exanthem
• Graft vs host disease

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Serious Adverse Cutaneous Reactions to Drugs

• Michael Bigby, MD
• Department of Dermatology
• Harvard Medical School and
• Beth Israel Deaconess Medical School
• Boston, MA
• mbigby_at_bidmc.harvard.edu