Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction that affects the skin and mucous membranes, including the mouth, eyes, and genitals. While SJS can sometimes be triggered by infections, a medication is the culprit in the majority of cases. The reaction typically begins with flu-like symptoms, followed by a painful rash that spreads and blisters, with the top layer of skin eventually shedding. An even more severe form, known as toxic epidermal necrolysis (TEN), involves greater skin detachment. Early identification and immediate withdrawal of the offending drug are crucial for a positive outcome. While numerous drugs are linked to SJS, some medication classes carry a higher risk than others.
High-Risk Medication Classes Associated with SJS
Allopurinol
Often prescribed for the prevention of gout, the drug allopurinol is a primary cause of SJS. The risk is particularly elevated in the first few months of treatment, with a stronger association observed when taking higher amounts. Genetic predisposition plays a significant role in allopurinol-induced SJS, particularly for individuals carrying the HLA-B58:01* allele. This allele is more common in populations of Han Chinese, Korean, and Thai descent, and screening is often recommended for these patients before starting allopurinol.
Anticonvulsants (Anti-seizure Medications)
Several anticonvulsant drugs used to treat epilepsy and mood disorders are frequently associated with SJS. The aromatic anticonvulsants are especially high-risk, including:
- Carbamazepine: Widely used but carries a well-known risk for SJS. A meta-analysis identified a significant association with specific human leukocyte antigen (HLA) variants.
- Lamotrigine: Risk is highest when starting treatment, especially when escalating the amount taken too quickly.
- Phenytoin and Phenobarbital: Both are older anticonvulsants that have been linked to SJS.
Sulfonamide Antibiotics
This class of antibiotics has a very high risk of inducing SJS. A meta-analysis of antibiotic-related SJS cases ranked sulfonamides as the most common culprits. Trimethoprim-sulfamethoxazole (e.g., Bactrim) is a well-known example within this group. Given the risk, clinicians are often advised to be judicious with their prescribing practices.
Other Implicated Medications
While the categories above are the most common, other medication classes also have documented links to SJS:
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Specific types, particularly the oxicam class, are associated with a large increase in SJS risk. Common examples include ibuprofen and naproxen.
- Nevirapine: This non-nucleoside reverse-transcriptase inhibitor, used in HIV treatment, is also recognized as a trigger for SJS.
- Antibiotics: Besides sulfonamides, other antibiotics like penicillins, cephalosporins, and minocycline have been implicated, although at a lower frequency.
Comparison of Major SJS Triggers
| Medication Category | Common Examples | Risk Period | Key Risk Factors | Genetic Link | Relative Risk |
|---|---|---|---|---|---|
| Allopurinol | Allopurinol (anti-gout) | First 2 months of therapy | Higher amounts, renal insufficiency | HLA-B58:01* (Asian populations) | High (Relative Risk: ~52) |
| Aromatic Anticonvulsants | Carbamazepine, Phenytoin, Lamotrigine | First 2 months of therapy | Rapid amount escalation (Lamotrigine) | HLA-B1502 (Asian populations), HLA-B58:01 | High (Relative Risk: ~90, 53) |
| Sulfonamide Antibiotics | Trimethoprim-sulfamethoxazole | Early weeks of therapy | Immunocompromised state (e.g., HIV) | Yes, several HLA variants implicated | Highest (Relative Risk: ~172) |
| Oxicam NSAIDs | Piroxicam | Early weeks of therapy | N/A | Less defined | High (Relative Risk: ~72) |
What to Do If You Suspect SJS
If you or someone you know shows signs of SJS, including flu-like symptoms followed by a spreading, blistering rash, it is a medical emergency requiring immediate attention. The single most important step is to stop the suspected medication and seek emergency medical care. Healthcare providers will need a detailed list of all medications, including recent changes, to identify and remove the offending agent. Treatment typically involves hospitalization, often in a specialized intensive care or burn unit, to provide supportive care similar to burn patients. This includes fluid replacement, nutrition, pain control, and specialized wound care to manage skin loss and prevent infection.
Conclusion
While many medications have the potential to cause SJS, allopurinol, certain anticonvulsants (like carbamazepine and lamotrigine), and sulfonamide antibiotics consistently stand out as some of the highest-risk culprits. Vigilance during the initial weeks of therapy, especially with these drug classes, is critical. Furthermore, genetic screening in high-risk populations can help prevent allopurinol-induced reactions. Awareness of the early flu-like symptoms and the blistering rash is key to prompt medical intervention, which significantly improves outcomes for this dangerous condition. For more detailed information on SJS management, consult authoritative medical resources such as the Merck Manuals.
