Sulfonamide Antibiotics: The Highest Risk
Extensive research consistently points to sulfonamide antibiotics as the class most frequently implicated in Stevens-Johnson syndrome (SJS). A key culprit within this class is trimethoprim-sulfamethoxazole, also known as co-trimoxazole. A 2025 analysis of the FDA Adverse Event Reporting System (FAERS) specifically identified sulfamethoxazole as presenting the highest risk signal for SJS/TEN among various antibiotics. This heightened risk is a well-documented concern for clinicians and patients, underscoring the importance of judicious use for these medications, particularly for specific indications and durations.
Other High-Risk Antibiotic Classes
While sulfonamides lead the list, other antibiotic classes are also known to cause SJS, though typically with a lower frequency. The risk profile for antibiotic-induced SJS, in descending order of frequency, generally includes:
- Penicillins: A major group of beta-lactam antibiotics, penicillins are frequently prescribed and are implicated in a significant portion of antibiotic-associated SJS cases. Examples include amoxicillin and amoxicillin-clavulanate.
- Cephalosporins: Another beta-lactam class, cephalosporins also carry a notable risk for SJS. Specific examples linked to SJS/TEN cases include cefuroxime and ceftriaxone. There is also a rare but life-threatening risk of cross-reactivity with penicillins for severe reactions like SJS.
- Fluoroquinolones: These broad-spectrum antibiotics have also been associated with SJS, though less commonly than sulfonamides and beta-lactams. Ciprofloxacin and levofloxacin are examples within this class.
- Macrolides: Representing a smaller proportion of cases, macrolides like azithromycin have also been linked to SJS.
Understanding the Mechanism: How SJS Develops
SJS is categorized as a severe cutaneous adverse reaction (SCAR) and is a type IV, T-cell-mediated delayed hypersensitivity reaction. It isn't a simple allergy but a complex, delayed immune response. The trigger, in this case an antibiotic, prompts an overreaction from the body's immune system, leading to widespread cell death in the skin and mucous membranes. This reaction is not immediate and typically manifests within one to a few weeks of starting the medication. In many cases, genetic factors, specifically certain human leukocyte antigen (HLA) polymorphisms, can predispose individuals to this reaction when exposed to certain medications.
Comparison of Antibiotic Classes and SJS Risk
| Antibiotic Class | Examples | Relative Risk Association (among antibiotics) |
|---|---|---|
| Sulfonamides | Trimethoprim-sulfamethoxazole, Sulfasalazine | Highest |
| Penicillins | Amoxicillin, Amoxicillin-clavulanate | High |
| Cephalosporins | Cefuroxime, Ceftriaxone | High |
| Fluoroquinolones | Ciprofloxacin, Levofloxacin | Moderate |
| Macrolides | Azithromycin | Lower |
Recognizing the Symptoms of Stevens-Johnson Syndrome
Early recognition is crucial for improving outcomes. Symptoms often begin with a non-specific illness resembling an upper respiratory infection before the characteristic rash appears.
- Initial symptoms: Fever, sore throat, headache, body aches, and fatigue.
- Progressive symptoms: A flat, red or purplish rash that can spread quickly across the face, trunk, and limbs.
- Blistering and skin detachment: The rash develops into painful blisters, and the epidermis begins to detach from the underlying dermis, often with lateral pressure (Nikolsky-positive sign).
- Mucosal involvement: Painful blisters and erosions can affect the mucous membranes of the mouth, throat, eyes, and genitals. This can cause severe pain and complications like vision impairment or difficulty eating.
Immediate Action for Suspected SJS
If you or someone you know shows any signs of SJS, take these steps immediately:
- Stop the medication immediately: Do not take any more doses of the suspected drug.
- Seek emergency medical care: This is a medical emergency that requires prompt evaluation and treatment.
- Inform healthcare providers: Clearly state all medications you have recently taken so the culprit drug can be identified and avoided in the future.
Key Risk Factors Beyond Antibiotic Type
While the specific antibiotic class is the primary factor, other elements can increase an individual's susceptibility to antibiotic-induced SJS:
- HIV/AIDS: Patients with HIV have a significantly higher risk of developing SJS compared to the general population.
- Genetic predisposition: Certain HLA genetic markers can make some individuals more susceptible to drug-induced SJS.
- Co-existing infections: Some infections, particularly certain viral or bacterial infections like Mycoplasma pneumoniae, can trigger SJS.
- Underlying medical conditions: A history of systemic lupus erythematosus, psoriasis, or malignancy has been associated with an increased SJS risk.
Conclusion
While a variety of antibiotics can trigger Stevens-Johnson syndrome, the sulfonamide class, and especially the drug trimethoprim-sulfamethoxazole, is most consistently and strongly linked to the condition. Other significant culprits include penicillins and cephalosporins. Given the rarity but high morbidity and mortality of SJS, it is crucial for both healthcare providers and patients to be aware of the risk factors and early symptoms. Prompt discontinuation of the offending medication is the most important step for treatment, and awareness of the causative agents is vital for prevention based on information from a systematic review and meta-analysis published in JAMA Dermatology.
