Which antibiotics are associated with Stevens-Johnson syndrome?

Antibiotics Associated with Stevens-Johnson Syndrome

Sulfonamide antibiotics are the most common antibiotics causing Stevens-Johnson syndrome (SJS), followed by penicillins, cephalosporins, fluoroquinolones, and macrolides. 1

High-Risk Antibiotics for SJS/TEN

Based on the most recent and comprehensive evidence, antibiotics associated with SJS/TEN include:

1. Sulfonamide antibiotics (highest risk):

   • Trimethoprim-sulfamethoxazole (co-trimoxazole)
   • Other sulfonamide antibiotics 2, 1

2. Beta-lactam antibiotics:

   • Penicillins (including amoxicillin and amoxicillin-clavulanate) 3, 1, 4
   • Aminopenicillins
   • Cephalosporins 1, 5

3. Other antibiotics:

   • Fluoroquinolones 1
   • Macrolides 1

Prevalence and Risk Assessment

According to the most recent systematic review and meta-analysis (2023), antibiotics are associated with 28% of all SJS/TEN cases worldwide 1. Among antibiotic-associated SJS/TEN:

• Sulfonamides: 32% of cases
• Penicillins: 22% of cases
• Cephalosporins: 11% of cases
• Fluoroquinolones: 4% of cases
• Macrolides: 2% of cases

Clinical Implications and Management

Recognition and Prevention

• SJS/TEN typically develops 5-28 days after starting a new medication 2
• Risk is higher in patients with previous drug hypersensitivity reactions to the same or similar drugs
• Genetic factors may increase susceptibility (e.g., HLA-B*1502 and carbamazepine in Han Chinese) 2, 5

Warning Signs of SJS/TEN

• Mucocutaneous tenderness
• Hemorrhagic erosions
• Erythema
• Epidermal detachment (blisters and denuded skin)
• Fever and flu-like symptoms often precede skin manifestations

Management of Suspected SJS/TEN

1. Immediate discontinuation of the suspected causative antibiotic 2
2. Urgent referral to specialized care (dermatology, burn center, or ICU) 2
3. Assessment of prognosis using SCORTEN 2
4. Supportive care and consideration of immunomodulating therapies

Special Considerations

Pediatric Patients

• In children, antibiotics and anticonvulsants are the most common causes of SJS/TEN 2
• Mycoplasma pneumoniae infection is a significant non-drug cause of SJS in children 2

Alternative Antibiotics

When treating patients with a history of SJS/TEN:

• Avoid the culprit antibiotic and structurally similar drugs
• Consider patch testing or T-cell proliferation assays in specialized centers to confirm the causative agent 2
• Choose antibiotics from a different class with no cross-reactivity

Pitfalls and Caveats

1. Delayed recognition: Early signs of SJS/TEN may be mistaken for common drug rashes or viral exanthems. Progressive mucosal involvement and skin pain (rather than itch) are concerning features.

2. Confounding factors: Paracetamol and ibuprofen are often considered as potential causes but may be confounders as they're frequently used to treat prodromal symptoms of SJS/TEN 2.

3. Infection vs. drug cause: Some cases of SJS/TEN, especially in children, may be triggered by infections rather than medications. Mycoplasma pneumoniae and Herpes simplex virus are documented causes 2, 5.

4. Mortality risk: SJS has a mortality rate of 1-5%, while TEN has a mortality rate of 25-35% 5. Prompt recognition and management are critical to improve outcomes.