What is Toxic Epidermal Necrolysis (TEN)?
Toxic epidermal necrolysis (TEN) is a rare, severe, and life-threatening dermatological condition characterized by widespread erythema, blistering, and detachment of the top layer of skin, the epidermis [1.5.3, 1.7.2]. It is considered a medical emergency often requiring treatment in a burn unit or intensive care unit (ICU) [1.5.7].
TEN is part of a spectrum of severe cutaneous adverse reactions (SCARs) that also includes Stevens-Johnson syndrome (SJS) [1.7.6]. The primary distinction between SJS and TEN is the percentage of body surface area (BSA) affected [1.7.3].
- Stevens-Johnson Syndrome (SJS): Skin detachment affects less than 10% of the BSA [1.7.2].
- SJS/TEN Overlap: Skin detachment is between 10% and 30% of the BSA [1.7.2].
- Toxic Epidermal Necrolysis (TEN): Skin detachment affects more than 30% of the BSA [1.7.2].
In addition to the skin, these conditions almost always affect mucous membranes, including the mouth, eyes, and genitals [1.7.6]. The mortality rate for TEN can be over 30%, making rapid diagnosis and management critical [1.2.2].
What is Metronidazole?
Metronidazole is a widely used antibiotic and antiprotozoal medication [1.6.4]. It is effective against anaerobic bacteria and certain parasites, making it a common treatment for infections in the gastrointestinal tract, skin, joints, and respiratory system [1.6.4]. While generally well-tolerated, it has a range of side effects from common (nausea, metallic taste) to rare but serious adverse events [1.6.3, 1.6.4].
The Link: Can Metronidazole Cause Toxic Epidermal Necrolysis?
Yes, though it is a very rare event, case reports have documented that metronidazole can cause toxic epidermal necrolysis [1.2.1, 1.2.5]. Medical literature contains several instances where metronidazole was identified as the likely causative agent in patients who developed TEN [1.2.1, 1.3.4]. In some reported cases, the causality was deemed "certain" based on diagnostic algorithms like the Naranjo algorithm [1.2.5].
It is important to note that while the association exists, metronidazole is not considered a high-risk drug for TEN compared to others [1.3.4]. Some research also highlights a significantly increased risk when metronidazole is used in combination with other drugs, such as mebendazole [1.2.2, 1.3.2]. However, reports confirm that metronidazole alone can, in rare instances, trigger SJS or TEN [1.3.1, 1.3.4].
Symptoms and Early Signs of SJS/TEN
Recognizing the early symptoms of SJS/TEN is crucial for a better prognosis. The reaction typically begins within one to three weeks after starting the offending medication [1.5.6].
Initial symptoms often mimic a flu-like illness (prodrome) and can include [1.5.2, 1.5.5]:
- Fever
- Sore throat, cough
- Malaise (general feeling of discomfort)
- Stinging or painful eyes
- Body aches
Following this initial phase, the characteristic skin and mucous membrane symptoms appear rapidly:
- A widespread, painful red or purplish rash that spreads and blisters [1.5.3].
- Formation of flaccid blisters that coalesce into large sheets of skin [1.5.2].
- Shedding of the skin, leaving raw, painful areas (denudation) [1.5.3].
- Positive Nikolsky sign, where gentle lateral pressure causes the epidermis to detach [1.5.2].
- Painful sores and erosions on mucous membranes, such as the mouth, lips, eyes, and genitals [1.5.6].
Diagnosis and Treatment
Diagnosis is primarily clinical, based on the patient's history (especially recent medication use), physical examination, and the characteristic skin lesions [1.3.4]. A skin biopsy can be performed to confirm the diagnosis and rule out other conditions [1.3.4].
The most critical first step in management is the immediate identification and withdrawal of the suspected causative drug [1.5.7]. Patients are typically admitted to a specialized unit, such as a burn center or ICU, for comprehensive supportive care [1.5.5].
Treatment focuses on:
- Fluid and Electrolyte Management: Replacing fluids lost through the denuded skin, similar to burn care [1.5.7].
- Wound Care: Using non-adherent dressings to protect the raw skin and prevent infection [1.5.2].
- Nutritional Support: Providing adequate nutrition, often via a nasogastric tube due to painful oral lesions, to support the hypercatabolic state and promote healing [1.5.2].
- Pain Management: Using analgesics, often opiates, to control the severe pain associated with the condition [1.5.2].
- Infection Prevention: Monitoring for and treating secondary infections, which are a major cause of mortality [1.5.2]. Prophylactic antibiotics are generally not recommended [1.5.2].
- Ophthalmology Care: Regular consultation with an ophthalmologist is mandatory to manage eye involvement and prevent long-term complications [1.5.7].
Comparing Drugs Known to Cause SJS/TEN
While many drugs have been implicated, some carry a much higher risk than others. Metronidazole is considered a low-risk or rare cause.
| Drug Class | Common Examples | Reported Risk of SJS/TEN |
|---|---|---|
| Anticonvulsants | Carbamazepine, Lamotrigine, Phenytoin | High [1.4.1, 1.4.8] |
| Allopurinol | Allopurinol | High [1.4.1, 1.4.4] |
| Sulfonamide Antibiotics | Sulfamethoxazole (often with Trimethoprim) | High [1.4.1, 1.4.8] |
| NSAIDs (Oxicam type) | Piroxicam, Meloxicam | Moderate [1.4.5, 1.4.8] |
| Other Antibiotics | Penicillins, Quinolones | Lower but significant [1.4.1, 1.4.8] |
| Metronidazole | Metronidazole | Very Rare [1.3.1, 1.3.4] |
Find more information at the National Center for Biotechnology Information (NCBI).
Conclusion
While metronidazole has been documented to cause toxic epidermal necrolysis, it is an extremely rare adverse reaction. The vast majority of patients who take metronidazole will not experience this severe complication. High-risk medications for TEN include certain anticonvulsants, allopurinol, and sulfonamide antibiotics. Nonetheless, the potential for this life-threatening reaction underscores the importance for both clinicians and patients to be vigilant. Recognizing the early flu-like symptoms followed by a painful rash is critical. Anyone who suspects they are having a severe skin reaction to any medication, including metronidazole, should seek immediate emergency medical care.
