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