A14. Drug allergy

Drug allergy

• Classification according to timeline
  • Immediate (< 1 hour)
    • Urticaria
    • Angioedema
    • Rhinitis
    • Bronchospasm
    • Anaphylaxis
  • Non-immediate (> 1 hour)
    • Delayed urticaria
    • Maculopapular exanthema
    • Erythroderma
    • Vasculitis
    • Stevens-Johnson syndrome (SJS)
    • Toxic epidermal necrolysis (TEN)
    • Drug reaction with eosinophilia and systemic symptoms (DRESS)
    • Acute generalized exanthematous pustulosis (AGEP)
    • Symmetrical drug-related intertriginous and flexural exanthemas (SDRIFE)
• Classification according to pathomechanism
  • Type I hypersensitivity
    • IgE-mediated mast cell activation as a reaction to a soluble antigen
    • All immediate drug allergies
    • Treatment
      • Eliminate culprit drug
      • Antihistamines
  • Type III hypersensitivity
    • IgG-mediated complement activation as a reaction to a soluble antigen
    • Vasculitis
    • Serum sickness
  • Type IVa hypersensitivity
    • Cell-mediated macrophage activation as a reaction to a presented antigen
    • Tuberculin reaction
    • Contact dermatitis
  • Type IVb hypersensitivity
    • Cell-mediated eosinophil activation as a reaction to a presented antigen
    • DRESS
    • Maculopapular exanthema
    • Erythroderma
  • Type IVc hypersensitivity
    • Cell-mediated T-cell activation as a reaction to a presented antigen
    • Stevens-Johnsons syndrome
    • Toxic epidermal necrolysis
  • Type IVd hypersensitivity
    • Cell-mediated neutrophils activation as a reaction to a presented antigen
    • AGEP
• Drug-induced urticaria
  • Drugs
    • Penicillin
    • Aspirin
    • NSAIDs
• Angioedema/Quincke-oedema
  • Drugs
    • NSAIDs
    • Aspirin
    • ACE-inhibitors (not technically a drug allergy)
  • Clinical features
    • Facial oedema
    • If laryngeal involvement – dyspnoea, inspiratory stridor
  • Treatment
    • Epinephrine
    • Steroids
    • Antihistamines
• Anaphylaxis
  • Drugs
    • Lidocaine
    • Anaesthetics
    • Aspirin
    • Contrast
    • NSAIDs
  • After minutes – hours
  • Clinical features
    • Hypotension
    • Bronchospasm, laryngeal oedema -> dyspnoea, inspiratory stridor
  • Treatment
    • Epinephrine
    • Steroids
    • Antihistamines
• Drug-induced vasculitis
  • Drugs
    • Antibiotics
    • Analgesics
  • Clinical features
    • Painful, palpable purpura
    • Urticaria
  • Resolve after drug cessation
• Serum sickness
  • Drugs
    • NSAIDs
    • Penicillins
  • Clinical features
    • Fever
    • Rash
    • Arthralgia
  • Resolve after drug cessation
• Maculopapular exanthema
  • On trunk, extremities
  • No eosinophilia
  • No systemic symptoms
  • Resolve after drug cessation
• Erythroderma
  • Erythema, scaling of the whole body
  • Eosinophilia
  • No systemic symptoms
  • Resolve after drug cessation

Severe cutaneous adverse reactions

• DRESS syndrome
  • Drug-related eosinophilia and systemic symptoms
    • Also called drug-induced hypersensitivity syndrome
  • Drugs
    • Allopurinol
    • Antiepileptics
    • Antibiotics
  • Risk factors
    • Older age
    • Renal failure
    • Certain HLA alleles
  • Clinical features
    • Fever
    • Pruritic morbilliform rash
    • Facial oedema
  • Multiorgan failure can occur
  • Fatal in 10%
  • Treatment
    • Drug cessation
    • Steroids
• Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)
  • If < 10% of skin surface is involved -> SJS
  • If 10 – 30% of skin surface is involved -> SJS/TEN overlap
  • If > 30% of skin surface is involved -> TEN
  • Drugs
    • Antibiotics
    • Antiepileptics
    • Sulpha drugs
    • Allopurinol
  • Risk factors
    • HIV infection
  • Clinical features
    • High fever
    • Painful erythematous macules
    • -> Lesions form bullae
    • -> Extensive, full-thickness epidermal necrosis and sloughing
    • Resembles superficial burns
    • Mucous membranes almost always involved
      • Stomatitis
      • Oral ulcers
      • Conjunctivitis
      • Urethritis
    • Circulatory shock
  • Diagnosis
    • Clinical
    • Positive Nikolsky sign
  • Treatment
    • Supportive care
    • Drug cessation
    • High-dose steroid
    • IV immunoglobulin
    • GM-CSF
  • Mortality 10 – 50%
• Acute generalized exanthematous pustulosis (AGEP)
  • Drugs
    • Penicillins
    • Quinolones
    • Sulpha drugs
  • Clinical features
    • Erythematous, oedematous pustules
    • Begin in intertriginous areas, progress over the whole body
    • Fever
  • Treatment
    • Drug cessation
    • Antipyretics
    • Oral steroids