A 28-year-old woman presents with fever, oral ulcers, and widespread blistering eruption involving 30% of body surface area. Histopathology shows full-thickness epidermal necrosis with subepidermal blister formation. Which is the most common causative drug in this patient?

Question

A 28-year-old woman presents with fever, oral ulcers, and widespread blistering eruption involving >30% of body surface area. Histopathology shows full-thickness epidermal necrosis with subepidermal blister formation. Which is the most common causative drug in this patient?

Accepted Answer

C. Antibiotics (sulfonamides, beta-lactams, fluoroquinolones). ## Most Common Drug Cause of SJS/TEN

**Key Point:** Antibiotics account for approximately 30–50% of all drug-induced SJS/TEN cases globally, with sulfonamides and beta-lactams being the leading agents [cite:Robbins 10e Ch 25].

### Epidemiology of Drug-Induced SJS/TEN

| Drug Class | Frequency | Notable Agents |
|---|---|---|
| **Antibiotics** | 30–50% | Sulfonamides, amoxicillin, cephalosporins, fluoroquinolones |
| Anticonvulsants | 15–20% | Phenytoin, carbamazepine, phenobarbital |
| Antiretrovirals | 5–10% | Nevirapine, abacavir |
| NSAIDs | 5–10% | Naproxen, ibuprofen, meloxicam |
| Allopurinol | 2–5% | Especially in renal impairment |

**High-Yield:** In India and other developing countries, sulfonamides (especially TMP-SMX) and beta-lactams remain the most frequent triggers because of their widespread use in primary care and infectious disease management [cite:Park 26e Ch 22].

### Pathomechanism

Drug-induced SJS/TEN occurs via:
1. Hapten formation: drug metabolites bind to keratinocytes
2. T-cell activation: CD8+ cytotoxic T cells recognize drug-peptide complex
3. Massive keratinocyte apoptosis: TNF-α, FasL, and perforin-mediated cell death
4. Epidermal-dermal separation: full-thickness necrosis in TEN

**Clinical Pearl:** The temporal relationship is critical—SJS/TEN typically develops 1–8 weeks after drug initiation, though re-exposure can trigger reaction within 24–48 hours.

### Risk Factors for Severe Reaction

- Genetic predisposition (HLA-B*1502 in carbamazepine; HLA-B*5801 in allopurinol)
- Renal/hepatic impairment (delayed drug clearance)
- Immunosuppression (HIV, malignancy)
- Polypharmacy (multiple culprit drugs possible)

**Warning:** Do not attribute all SJS/TEN to anticonvulsants or antiretrovirals—antibiotics are statistically more common and should be the first consideration in a drug-induced case.

Answer

A. NSAIDs (naproxen, ibuprofen)

Answer

B. Antiretrovirals (nevirapine, abacavir)

Answer

D. Anticonvulsants (phenytoin, carbamazepine)

A 28-year-old woman presents with fever, oral ulcers, and widespread blistering eruption involving >30% of body surface area. Histopathology shows full-thickness epidermal necrosis with subepidermal blister formation. Which is the most common causative drug in this patient?

Explanation

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