Medications That Cause Stevens-Johnson Syndrome
The most common medications causing Stevens-Johnson syndrome (SJS) are anticonvulsants (carbamazepine, lamotrigine, phenytoin, phenobarbital), antibiotics (particularly sulfonamides), allopurinol, nevirapine, and oxicam-type NSAIDs. 1
High-Risk Medications
Anticonvulsants
- Carbamazepine - Particularly high risk in patients of Southeast Asian descent with HLA-B*1502 genetic marker 2, 3
- Lamotrigine - Associated with a relative risk >14 4
- Phenytoin - Can cause serious skin reactions including SJS/TEN 5
- Phenobarbital - Well-documented association 1
Antibiotics
- Sulfamethoxazole and other sulfonamide antibiotics - Among the most common causes 1, 6
- Aminopenicillins - Associated with increased risk 6
- Cephalosporins - Documented risk 3
- Quinolones - Associated with SJS/TEN 3, 6
Other High-Risk Medications
- Allopurinol - Particularly at doses above 100mg daily 7, 6
- Nevirapine - Very high risk with relative risk >22 8, 4
- Oxicam-type NSAIDs - Strong association 1, 6
- Sulfasalazine - Well-documented risk 1, 3
Medications with Emerging Risk
- Sertraline - Relative risk of 11 4
- Pantoprazole - Relative risk of 18 4
- Tramadol - Relative risk of 20 4
- Efavirenz - Associated with rash that can progress to SJS 8
Genetic Risk Factors
Certain genetic markers significantly increase the risk of SJS/TEN with specific medications:
- HLA-B*1502 - Strong association with carbamazepine-induced SJS/TEN in patients of Southeast Asian ancestry 2, 5, 7
- Genetic testing is recommended before prescribing carbamazepine to patients of Southeast Asian descent 3
Timing of Reaction
- Most reactions occur within 5-28 days after starting the medication 1
- Risk is highest during the first few weeks of drug intake 4
- Shorter latency period may occur in patients with previous exposure to the same drug 1
Special Considerations
Children
- In the pediatric population, both infections (particularly Mycoplasma pneumoniae) and medications are important triggers of SJS/TEN 2
- Anticonvulsants and antibiotics are the most commonly implicated medications in children 2
- Paracetamol (acetaminophen) and ibuprofen have unclear associations and may be confounders due to their use in treating prodromal symptoms 2
Risk Assessment
- The SCORTEN score should be calculated within the first 24 hours of admission to predict mortality 1
- Immediate withdrawal of the suspected medication is crucial as it decreases the risk of death 2
Prevention Strategies
- Avoid high-risk medications when safer alternatives exist 4
- Consider genetic testing for HLA-B*1502 in patients of Southeast Asian ancestry before prescribing carbamazepine 5, 7
- In patients with a history of SJS/TEN, avoid not only the causative medication but also those with similar chemical structures 3
Diagnostic Challenges
- Differentiating between early drug-associated rash and acute seroconversion can be difficult 8
- Document all medications taken by the patient in the 2 months prior to symptom onset 1
- Establish a timeline for each medication to help identify the culprit drug 1
SJS/TEN are severe and potentially fatal conditions with mortality rates of 1-5% for SJS and 25-35% for TEN 6. Early recognition of the causative medication and prompt discontinuation are essential for improving outcomes.