Stevens-Johnson syndrome (SJS) and its more severe form, toxic epidermal necrolysis (TEN), are rare but life-threatening hypersensitivity reactions that primarily affect the skin and mucous membranes. The condition often starts with flu-like symptoms before progressing to a painful rash that spreads and blisters, leading to the top layer of skin dying and shedding. While SJS can be caused by infections, drug reactions are the most frequent trigger in adults. However, identifying a single "most common" drug trigger is complex, as the data can vary depending on the patient population, prescribing habits, and specific study methodology. Several classes of medication are consistently identified as major culprits, with certain individual drugs within these classes carrying a particularly high risk.
Sulfonamide Antibiotics: A Leading Culprit
For many years, sulfonamide antibiotics have been heavily implicated in triggering SJS/TEN. A 2023 meta-analysis confirmed that among antibiotic-associated SJS/TEN cases, the sulfonamide class was responsible for the largest percentage of incidents, at 32%. The most notable drug in this category is trimethoprim-sulfamethoxazole, commonly known as Bactrim or Septra. The risk is particularly elevated in HIV-positive patients, where the incidence of SJS is about 100 times greater than in the general population. The high risk associated with sulfonamides highlights the importance of judicious use and careful consideration of alternative antibiotics when possible.
Anticonvulsants: Significant Triggers
Anticonvulsant medications, used to treat seizures and other neurological conditions, are another major class of drugs strongly linked to SJS. In a 2022 review of US cases, anticonvulsants were identified as the most probable culprit drug class in 30% of cases. Key drugs within this category include:
- Carbamazepine: Risk is significantly increased in patients with the genetic marker HLA-B*1502, particularly those of Asian ancestry. The U.S. Food and Drug Administration (FDA) recommends screening these individuals before starting treatment.
- Lamotrigine: Known for a high association with SJS, especially when initiated with higher-than-recommended doses or rapid titration. Children are also at a higher risk.
- Phenytoin: Another older anticonvulsant with a long-standing association with SJS and TEN.
Allopurinol: A Dose and Genetic Dependent Risk
Allopurinol, a medication widely used to treat gout and kidney stones, is a frequent and significant cause of SJS/TEN. This risk is heightened by several factors:
- Higher Doses: Taking higher doses of allopurinol, especially more than 100 mg per day, is associated with a greater risk. Starting with a low dose and titrating slowly is recommended.
- Genetic Predisposition: A strong association exists between allopurinol-induced SJS/TEN and the HLA-B*5801 allele. This genetic marker is more prevalent in individuals of Han Chinese, Thai, and Korean descent. Screening for this allele can help identify and manage high-risk patients.
- Renal Impairment: Patients with impaired kidney function are at higher risk because allopurinol's active metabolite, oxypurinol, accumulates in the body.
Comparison of High-Risk SJS/TEN Drug Triggers
| Drug Type | Key Examples | Associated Genetic Factor | Risk Profile / Notes |
|---|---|---|---|
| Sulfonamide Antibiotics | Trimethoprim-sulfamethoxazole, sulfasalazine | Higher risk in HIV-positive patients. | Among antibiotics, this class has the highest risk. Important to consider antibiotic stewardship. |
| Anticonvulsants | Carbamazepine, lamotrigine, phenytoin | HLA-B*1502 (Carbamazepine in Asians). | Overall high-risk class, with individual drugs showing varying risk profiles. Dose titration matters. |
| Allopurinol | Allopurinol (for gout) | HLA-B*5801 (esp. Han Chinese, Thai, Korean). | Risk increases with higher dosage and pre-existing renal impairment. Genetic screening is recommended for certain populations. |
| NSAIDs | Ibuprofen, naproxen, oxicams | None well-established for all NSAIDs. | Generally lower risk than other classes, but specific drugs like oxicams may have higher risk. |
Other Implicated Medications and Risk Factors
While sulfonamides, anticonvulsants, and allopurinol represent the most common drug triggers, several other medications have also been linked to SJS/TEN, including:
- Nevirapine: An antiretroviral drug used to treat HIV.
- Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Specific types, especially oxicams (like piroxicam), and even commonly used medications like ibuprofen and acetaminophen.
- Herbal Remedies and Contrast Media: In some cases, SJS has been linked to these agents.
Apart from drug exposure, other risk factors can increase a person's susceptibility to SJS/TEN:
- HIV infection
- Weakened immune system due to conditions like organ transplants, cancer (especially blood cancer), or autoimmune diseases.
- A personal or family history of SJS/TEN.
- Certain viral infections, like Mycoplasma pneumoniae or herpes simplex virus.
Conclusion
While it is difficult to pinpoint a single most common drug trigger for Stevens-Johnson syndrome, the medication classes most frequently associated with this severe reaction are sulfonamide antibiotics, anticonvulsants, and allopurinol. High-risk drugs such as trimethoprim-sulfamethoxazole, carbamazepine, and allopurinol are particularly significant, with genetic predisposition and patient-specific risk factors playing a critical role in susceptibility. Patients should be aware of the early, flu-like warning signs and seek immediate medical attention if a drug reaction is suspected. Timely discontinuation of the offending drug is the cornerstone of treatment and the most important factor in improving outcomes and preventing life-threatening complications. For more comprehensive information, the CDC offers extensive resources on various adverse drug events, including SJS [cdc.gov].
