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What Antibiotics Cause Stevens-Johnson Syndrome?

4 min read

According to a 2023 meta-analysis, antibiotics are associated with more than one-quarter of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) cases worldwide. This life-threatening hypersensitivity reaction can be triggered by several common medication classes, and it is crucial for both healthcare providers and patients to understand what antibiotics cause Stevens-Johnson syndrome.

Quick Summary

Stevens-Johnson syndrome (SJS) is a rare, severe skin reaction often triggered by certain antibiotics. Key culprits include sulfonamides, penicillins, and cephalosporins, with immediate discontinuation being the most critical treatment step.

Key Points

  • Leading antibiotic culprits: Sulfonamides (e.g., trimethoprim-sulfamethoxazole) carry the highest risk among antibiotics for causing SJS.

  • Other implicated classes: Penicillins, cephalosporins, fluoroquinolones, and macrolides have also been associated with SJS, although less frequently.

  • High-risk populations: Patients with HIV are at a significantly higher risk of developing SJS, especially when taking sulfonamide-based prophylaxis.

  • Recognizing symptoms: SJS begins with flu-like symptoms followed by a painful, blistering, and shedding rash that affects the skin and mucous membranes.

  • Immediate action is vital: The first and most critical step in managing SJS is immediately discontinuing the causative medication and seeking urgent medical care.

  • Distinction from TEN: SJS is a less severe form of a broader condition, with Toxic Epidermal Necrolysis (TEN) involving more extensive skin detachment and higher mortality.

  • Genetic predispositions exist: Some individuals have genetic markers (like certain HLA alleles) that can increase their risk for SJS with specific drugs, although this is more established for some non-antibiotic drugs.

In This Article

What is Stevens-Johnson Syndrome (SJS)?

Stevens-Johnson syndrome (SJS) is a rare and severe disorder affecting the skin and mucous membranes, which are the linings of internal organs and body cavities. It is often triggered by an adverse reaction to a medication, though infections can also be a cause. SJS is part of a spectrum of diseases, with the most severe form being toxic epidermal necrolysis (TEN), which involves the shedding of larger areas of the skin. The condition typically begins with non-specific, flu-like symptoms, followed by a painful, widespread red or purple rash that blisters and then sheds. The progression is often rapid, making timely diagnosis and intervention critical. The mortality rate is low for SJS but significantly higher for TEN.

Leading Antibiotic Culprits in SJS

Medical studies and meta-analyses have identified several classes of antibiotics that are most frequently implicated in triggering SJS. While the risk is generally very low for any individual, understanding the highest-risk classes is important for making informed healthcare decisions.

  • Sulfonamides: This class, especially the combination of trimethoprim-sulfamethoxazole (e.g., Bactrim), is the most common antibiotic cause of SJS. A 2023 meta-analysis found that sulfonamides were associated with 32% of antibiotic-linked SJS cases. The risk is particularly heightened in certain patient populations, such as those with HIV.
  • Penicillins: As one of the most widely used antibiotic classes, penicillins are also significant culprits, contributing to approximately 22% of antibiotic-associated SJS cases in the same meta-analysis. Specific penicillins linked to SJS include amoxicillin and ampicillin.
  • Cephalosporins: This class of beta-lactam antibiotics, which is structurally related to penicillin, has also been shown to cause SJS. The meta-analysis indicated cephalosporins were implicated in 11% of antibiotic-linked SJS cases. Examples include ceftriaxone, cefuroxime, and cefotaxime.

Other Antibiotic Classes Associated with SJS

While less frequent than the leading culprits, other antibiotic classes have been associated with SJS, highlighting that nearly any antibiotic can potentially trigger the reaction, although the risk level varies significantly.

  • Fluoroquinolones: These antibiotics, which include drugs like ciprofloxacin and levofloxacin, are also known to be potential triggers for SJS. Their overall contribution to antibiotic-associated SJS cases is lower, at around 4%.
  • Macrolides: Including drugs such as azithromycin, macrolides represent a small proportion of antibiotic-linked SJS cases, roughly 2%.
  • Others: Other antibiotics occasionally implicated include vancomycin and gentamicin.

Recognizing Stevens-Johnson Syndrome

Early recognition and discontinuation of the offending drug are paramount in treating SJS and reducing its severity. The condition typically presents in two phases:

  1. Prodrome Phase: This occurs one to three days before the rash appears and involves flu-like symptoms. These can include fever, sore throat, fatigue, and burning eyes.
  2. Eruptive Phase: The rash begins as red or purple macules (flat spots) that spread and coalesce. Blisters then form on the skin and mucous membranes, including the mouth, nose, eyes, and genitals. Eventually, the top layer of the skin begins to shed.

Comparison of SJS Risk by Antibiotic Class

Antibiotic Class Relative Risk Level Specific Drug Examples Notes
Sulfonamides Highest Trimethoprim-sulfamethoxazole (Bactrim) Elevated risk, particularly in HIV patients.
Penicillins High Amoxicillin, Ampicillin Significant contributor due to high usage rates.
Cephalosporins Moderate Ceftriaxone, Cefuroxime Shares a structural similarity with penicillins.
Fluoroquinolones Low Ciprofloxacin (Cipro), Levofloxacin Widely prescribed but lower incidence of SJS compared to sulfonamides.
Macrolides Very Low Azithromycin Lowest reported frequency among common implicated antibiotics.

Risk Factors for SJS

Several factors can increase an individual's susceptibility to drug-induced SJS:

  • HIV/AIDS: Individuals with HIV/AIDS, particularly when taking certain antibiotics like trimethoprim-sulfamethoxazole for prophylaxis, have a significantly higher incidence of SJS.
  • Genetic Factors: Specific human leukocyte antigen (HLA) alleles are known to predispose certain ethnic populations to SJS from particular medications. For instance, the HLA-B*15:02 allele is strongly associated with SJS caused by carbamazepine in some Asian populations, though links with antibiotics are also being studied.
  • Other Medications: Other non-antibiotic drugs, such as allopurinol (for gout) and certain anticonvulsants (like phenytoin), are also major triggers for SJS. Simultaneous use of multiple high-risk medications can increase complexity in identifying the culprit.
  • Infections: Although most cases are drug-related, infections can trigger SJS, with Mycoplasma pneumoniae and herpes simplex virus being among the reported causes.

Conclusion

While Stevens-Johnson syndrome is a rare and unpredictable condition, it is a severe hypersensitivity reaction that can be triggered by antibiotics. A wide range of antibiotic classes, most notably sulfonamides, penicillins, and cephalosporins, have been implicated. The most crucial step in management is the immediate discontinuation of the suspected medication. Given the high morbidity and mortality associated with SJS and TEN, awareness of the potential risks and early recognition of symptoms are essential. Healthcare professionals must weigh the benefits against the risks, and patients should be educated on the warning signs to ensure prompt medical attention if a reaction occurs.

For more detailed information, consult the Merck Manual on Stevens-Johnson Syndrome.

Frequently Asked Questions

Sulfonamide antibiotics, particularly trimethoprim-sulfamethoxazole, are the most common cause of antibiotic-induced Stevens-Johnson syndrome.

Yes, penicillins are one of the most frequently implicated antibiotic classes, with specific drugs like amoxicillin and ampicillin known to cause SJS in some individuals.

The first signs of SJS often include flu-like symptoms such as a fever, sore throat, fatigue, and burning eyes, which can appear one to three days before a painful rash begins.

A reaction can occur while taking the antibiotic or up to two weeks after stopping it. The onset of SJS is typically within the first two months of starting a new medication.

While a single drug is most often the cause, SJS can be triggered by multiple drugs simultaneously. Healthcare providers use a tool called the ALDEN score to help identify the most likely culprit when multiple drugs are involved.

If you suspect SJS, you should stop taking the suspected medication immediately and seek emergency medical care, as the condition requires urgent hospitalization and treatment.

Yes, individuals with HIV are at a significantly higher risk, especially when using trimethoprim-sulfamethoxazole. Certain genetic predispositions can also increase risk in specific populations.

References

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Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice.