Can Aminoglycosides Cause Steven Johnson Syndrome? An In-depth Analysis

October 13, 2025 •

4 min read

While severe drug-induced skin reactions are rare, recent pharmacovigilance studies have detected signals linking aminoglycosides to Stevens-Johnson syndrome (SJS) and its more severe form, toxic epidermal necrolysis (TEN). Although historically not considered a primary culprit like sulfa drugs or anticonvulsants, new evidence suggests that these antibiotics, including gentamicin, may increase the risk of developing this potentially fatal skin condition.

Quick Summary

An examination of the potential association between aminoglycoside antibiotics and the serious skin disorder Stevens-Johnson syndrome, highlighting the emerging risk signals from recent research and the need for clinical vigilance.

Key Points

Emerging Link: Recent large-scale pharmacovigilance studies indicate a potential, albeit low, risk of aminoglycosides causing Stevens-Johnson syndrome (SJS).
Primary Adverse Effects: Aminoglycosides are more commonly associated with severe nephrotoxicity (kidney damage) and ototoxicity (ear damage).
Rare but Severe: SJS/TEN is a rare but life-threatening immune-mediated reaction involving severe skin and mucous membrane blistering and shedding.
Immunological Trigger: The mechanism is thought to involve a T-cell-mediated immune response, where the drug acts as an antigen triggering widespread cell death.
Clinical Vigilance is Key: Early recognition of flu-like symptoms and a spreading rash in patients on aminoglycosides is crucial for prompt action and improved outcomes.
Other Reactions: Aminoglycosides have also been reported to cause other hypersensitivity reactions, such as allergic contact dermatitis and DRESS syndrome.
Comparative Risk: The risk of SJS from aminoglycosides appears significantly lower than from other high-risk drug classes like sulfonamides and certain anticonvulsants.
Patient History Matters: A history of hypersensitivity reactions to one aminoglycoside may lead to cross-reactivity with others due to similar chemical structures.

Understanding Aminoglycosides and Stevens-Johnson Syndrome

Aminoglycosides are a class of potent, broad-spectrum antibiotics primarily used for treating severe, life-threatening infections caused by aerobic gram-negative bacteria, such as Pseudomonas aeruginosa. Common examples include gentamicin, tobramycin, and amikacin. Despite their efficacy, aminoglycosides are known for their potential for serious adverse effects, most notably nephrotoxicity (kidney damage) and ototoxicity (ear damage).

Steven Johnson Syndrome (SJS), and its more severe counterpart Toxic Epidermal Necrolysis (TEN), are rare but severe mucocutaneous reactions that are most commonly triggered by medications. SJS is characterized by flu-like symptoms followed by a painful, blistering rash and subsequent shedding of the skin. It is a medical emergency requiring hospitalization, often in a burn unit, due to the extensive skin and mucous membrane damage.

Historical and Emerging Links

For many years, the primary drug culprits for SJS have been well-established, including sulfonamide antibiotics, certain anticonvulsants (lamotrigine, carbamazepine), and allopurinol. Aminoglycosides were not typically classified among the high-risk medications for this condition. However, a growing body of evidence, especially from large-scale pharmacovigilance studies, has started to change this perception.

The Shift in Clinical Understanding

Emerging studies using large claims databases and adverse event reporting systems have begun to signal an association that warrants increased clinical caution. For instance, a recent case-crossover study utilizing a Japanese claims database found an increased odds ratio for SJS/TEN associated with the use of several antibiotic classes, including aminoglycosides. While the exact mechanisms are still under investigation, these studies suggest that the risk, while low compared to other drug classes, is non-zero and requires recognition. Another study in 2024, using data from the FDA Adverse Event Reporting System (FAERS), identified gentamicin among several antibiotics with significant risk associations for SJS/TEN.

The Mechanisms Behind Drug-Induced SJS

The precise pathophysiology of SJS is not fully understood but is believed to involve a cytotoxic T-cell-mediated immune response. In this process, the body's T-cells mistakenly identify drug antigens on skin keratinocytes as a threat, triggering a widespread apoptotic (programmed cell death) cascade. Contributing factors include:

Genetic Predisposition: Certain genetic variations, particularly in human leukocyte antigens (HLAs), can increase a person's risk of developing SJS in response to certain medications.
Immune System Factors: The drug is thought to act as a hapten or pro-hapten, binding to a carrier protein and becoming an immunogenic antigen. This triggers a T-cell-mediated immune reaction that leads to cell death.

While the main pharmacological adverse effects of aminoglycosides are related to their concentration-dependent toxicity on the kidneys and ears, their capacity to trigger hypersensitivity reactions has also been documented, albeit rarely. Cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been associated with aminoglycosides, indicating their potential to cause severe systemic immune responses. This immunological potential supports the plausibility of their involvement in SJS/TEN, even if at a lower incidence than other drug classes.

Aminoglycoside Adverse Effects: A Comparative Perspective

While the risk of SJS/TEN is a serious concern, it is important to contextualize it within the broader spectrum of aminoglycoside adverse effects. The table below compares the more common and historically recognized side effects with the more recently identified risk of SJS/TEN.


Adverse Effect	Incidence Rate	Mechanism	Reversibility	Monitoring	Severity
Nephrotoxicity	10–25% of patients	Accumulation in renal proximal tubular cells, causing apoptosis	Often reversible with discontinuation	Routine serum creatinine and urea monitoring	High
Ototoxicity	2–45% of patients	Damage to sensory cells of the inner ear	Often irreversible	Auditory and vestibular function monitoring	High
SJS/TEN	Very low, emerging reports	Cytotoxic T-cell-mediated immune response leading to keratinocyte apoptosis	Variable, potential for long-term complications	Clinical observation for flu-like symptoms, rash	Extremely High

Clinical Implications and Patient Management

The emerging association between aminoglycosides and SJS/TEN has significant implications for clinical practice. Healthcare providers should be aware of this potential risk, especially when prescribing these antibiotics. Important considerations for patient management include:

Risk Assessment: Carefully weigh the benefits of aminoglycoside therapy against the risks, particularly in patients with a history of severe cutaneous adverse reactions or known genetic predispositions.
Patient Education: Inform patients about the potential for adverse drug reactions, including skin-related issues. Educate them on the early signs of SJS/TEN, such as flu-like symptoms followed by a rash.
Prompt Recognition: Any patient on aminoglycoside therapy who develops a rash should be immediately and thoroughly evaluated. Early detection and discontinuation of the offending drug are critical for improving outcomes.
Alternative Therapies: In cases where a risk of SJS is suspected or confirmed, or if a patient has a history of hypersensitivity to this class, alternative antibiotic therapies should be considered.
Continued Vigilance: Healthcare professionals and pharmacovigilance systems should continue to monitor and report adverse events to enhance the collective understanding of drug-induced SJS/TEN.

Conclusion

While aminoglycosides have primarily been associated with nephrotoxicity and ototoxicity, recent real-world data and pharmacovigilance studies suggest they can also be implicated in the development of Stevens-Johnson syndrome. The risk is considered low compared to other drug classes, but it is not negligible. This evolving understanding highlights the importance of clinical vigilance and emphasizes that no drug is completely without risk. By remaining informed of these emerging risks and promptly responding to potential adverse reactions, healthcare providers can help mitigate the devastating consequences of SJS for their patients. Further research with larger sample sizes is warranted to better characterize this association and its specific risk factors.

For a detailed analysis of drug-induced SJS, including known high-risk medications, the NIH website offers a comprehensive overview.

Frequently Asked Questions

Aminoglycosides, such as gentamicin, tobramycin, and amikacin, are used to treat serious bacterial infections, particularly those caused by aerobic gram-negative bacteria like Pseudomonas aeruginosa.

The most common and serious side effects of aminoglycosides are kidney damage (nephrotoxicity) and inner ear damage (ototoxicity), which can lead to hearing loss or balance issues.

SJS caused by aminoglycosides is very rare. However, recent large-scale studies have shown an emerging, albeit small, risk signal that warrants clinical awareness.

SJS often begins with flu-like symptoms, including fever, sore mouth and throat, and fatigue, which are followed by a widespread, painful, red or purple rash and blistering.

If SJS is suspected, seek immediate medical attention. It is a medical emergency that requires prompt diagnosis and hospitalization. The suspected medication should be discontinued immediately.

The course of SJS is variable. The affected skin often regrows, but complications such as scarring, permanent eye problems, and lung damage can occur. Early intervention improves the prognosis.

Yes, other hypersensitivity reactions have been reported, including allergic contact dermatitis (especially with topical use of neomycin) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).