What medications cause Stevens-Johnson syndrome?

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 1, 2
• Lamotrigine - Associated with a relative risk >14 3
• Phenytoin - Can cause serious skin reactions including SJS/TEN 4
• Phenobarbital - Well-documented association 1

Antibiotics

• Sulfamethoxazole and other sulfonamide antibiotics - Among the most common causes 1, 5
• Aminopenicillins - Associated with increased risk 5
• Cephalosporins - Documented risk 2
• Quinolones - Associated with SJS/TEN 2, 5

Other High-Risk Medications

• Allopurinol - Particularly at doses above 100mg daily 6, 5
• Nevirapine - Very high risk with relative risk >22 1, 3
• Oxicam-type NSAIDs - Strong association 1, 5
• Sulfasalazine - Well-documented risk 1, 2

Medications with Emerging Risk

• Sertraline - Relative risk of 11 3
• Pantoprazole - Relative risk of 18 3
• Tramadol - Relative risk of 20 3
• Efavirenz - Associated with rash that can progress to SJS 1

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 1, 4, 6
• Genetic testing is recommended before prescribing carbamazepine to patients of Southeast Asian descent 2

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 3
• 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 1
• Anticonvulsants and antibiotics are the most commonly implicated medications in children 1
• Paracetamol (acetaminophen) and ibuprofen have unclear associations and may be confounders due to their use in treating prodromal symptoms 1

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 1

Prevention Strategies

• Avoid high-risk medications when safer alternatives exist 3
• Consider genetic testing for HLA-B*1502 in patients of Southeast Asian ancestry before prescribing carbamazepine 4, 6
• In patients with a history of SJS/TEN, avoid not only the causative medication but also those with similar chemical structures 2

Diagnostic Challenges

• Differentiating between early drug-associated rash and acute seroconversion can be difficult 1
• 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 5. Early recognition of the causative medication and prompt discontinuation are essential for improving outcomes.