Drug Allergies

Drug Allergy Basics - Reaction Riddles

• Immune-mediated adverse drug reactions (ADRs); distinct from predictable side effects (Type A reactions).
• Hapten Concept: Most drugs are small molecules (< 1 kDa) acting as haptens; they bind to carrier proteins (e.g., albumin) to become immunogenic.
• Gell & Coombs Classification in Drug Allergy:
  • Type I (IgE-mediated, Immediate): Anaphylaxis, urticaria, angioedema. Onset: minutes to <1-2 hours.
  • Type II (Cytotoxic, IgG/IgM): Drug-induced hemolytic anemia, thrombocytopenia. Variable onset.
  • Type III (Immune Complex, IgG): Serum sickness, vasculitis, drug fever. Onset: 1-3 weeks.
  • Type IV (T-cell mediated, Delayed):
    • IVa (Th1): Tuberculin-type reaction, contact dermatitis.
    • IVb (Th2): Maculopapular exanthems, DRESS syndrome.
    • IVc (Cytotoxic T-cells): Bullous exanthems like SJS/TEN.
    • IVd (Neutrophilic): Acute Generalized Exanthematous Pustulosis (AGEP).
• Pseudoallergy (Non-immune anaphylaxis): Direct mast cell degranulation (e.g., opiates, radiocontrast media, vancomycin - Red Man Syndrome). No prior sensitization needed.

⭐ Penicillins are notorious for eliciting all four types of Gell & Coombs hypersensitivity reactions, making them a versatile allergen model.

Culprit Drugs & Syndromes - Pill Perils

• Common Culprits:

  • Antibiotics: Beta-lactams (Penicillins, Cephalosporins), Sulfonamides.
  • NSAIDs: Ibuprofen, Aspirin.
  • Anticonvulsants: Carbamazepine, Phenytoin, Lamotrigine.
  • 📌 Mnemonic: "ABC-S" (Antibiotics, Barbiturates/Anticonvulsants, Contrast, Sulfa/Salicylates).

• Key Syndromes:

  • Anaphylaxis: Acute, IgE-mediated, life-threatening.
  • Urticaria/Angioedema: Wheals, localized swelling.
  • SJS/TEN: Mucocutaneous blistering. SJS <10% BSA, TEN >30% BSA, Overlap 10-30%.
  • DRESS: Rash, Eosinophilia, Systemic Symptoms (fever, organ involvement). Latency 2-8 wks.
  • SSLR (Serum Sickness-Like Reaction): Fever, rash, arthralgia. Cefaclor common.
  • FDE (Fixed Drug Eruption): Recurring localized plaques on re-exposure.

⭐ Carbamazepine, phenytoin, and lamotrigine are high-risk for SJS/TEN and DRESS. HLA-B* 1502 (Asians) linked to carbamazepine-SJS/TEN.

Diagnosis Deep Dive - Clue Collection

• Detailed History: Cornerstone!
  • Suspect drug: name, dose, route, timing.
  • Previous exposures & reactions to any drug.
  • Reaction details: onset, duration, morphology, severity.
• Skin Tests:
  • SPT & IDT: Immediate (Type I, e.g., penicillins). Read: 15-20 min.
  • Patch Test: Delayed (Type IV, e.g., SJS/DRESS). Read: 48h, 72-96h.
• In-vitro Tests:
  • sIgE: Limited drugs (e.g., penicillin, muscle relaxants).
  • BAT, LTT: Specialized, less routine; research value.
• Drug Provocation Test (DPT):
  • Gold standard to confirm/exclude allergy.
  • Graded doses of suspect drug, supervised.
  • ⚠️ High risk; controlled settings only, by experts.

⭐ DPT contraindicated for prior life-threatening reactions (e.g., anaphylaxis, severe exfoliative dermatitis like SJS/TEN).

Management & Prevention - Reaction Rescue

• Immediate Actions:
  • STOP offending drug.
  • ABCDE assessment.
• Anaphylaxis Management:
  • Epinephrine (Adrenaline) IM: 0.01 mg/kg (1:1000 sol.) (max 0.3-0.5 mg). Repeat 5-15 min PRN.
  • Antihistamines (H1 blockers, e.g. cetirizine).
  • Corticosteroids (e.g., Hydrocortisone IV/IM) - prevent biphasic.
  • Oxygen, IV fluids.

• Severe Reactions (SCARs):
  • SJS/TEN: Urgent supportive care, ophthalmology.
  • DRESS: Systemic corticosteroids, monitor organs.
• Post-Reaction/Prevention:
  • Drug withdrawal.
  • Use unrelated alternative drugs.
  • Desensitization: If drug essential (IgE-mediated); specialist.
  • Prevention: Detailed allergy history, clear documentation (allergy card/bracelet), consider pre-testing (e.g., penicillin skin test).

⭐ Epinephrine: first-line for anaphylaxis. Administer IM (anterolateral thigh). Dose: 0.01 mg/kg (max 0.5 mg).

High‑Yield Points - ⚡ Biggest Takeaways

• Beta-lactams (penicillins) and NSAIDs are common culprits in pediatric drug allergies.
• Anaphylaxis, an IgE-mediated reaction, requires immediate epinephrine.
• SJS/TEN and DRESS are critical non-IgE mediated (delayed) reactions.
• Clinical history is key; skin tests for Type I. DPT is gold standard but risky.
• Consider beta-lactam cross-reactivity: low with 2nd/3rd gen cephalosporins; aztreonam generally safe with penicillin allergy.
• Serum sickness-like reactions (fever, rash, arthralgia) typically occur 1-3 weeks post-drug.