What is Toxic Epidermal Necrolysis?

  • Ezgi Uslu Icli Medical Doctor - Gazi University Medical School, Turkey

Not every skin condition is considered to be minor. In fact, some could be potentially life-threatening, and toxic epidermal necrolysis (TEN) is one of them.

Toxic epidermal necrolysis  is defined as the separation of the outermost layer of the skin from the underlying skin, which may cause serious systemic infection leading to sepsis and death.1

It is very important to know how to recognise TEN and act properly in order to improve the outcomes. You can increase your knowledge and find answers to your questions about TEN by reading this article, where we will provide valuable and relevant information on all aspects of this health issue.


TEN and Stevens-Johnson syndrome (SJS) are both serious and potentially life-threatening skin conditions. They both affect the epidermis and mucous membranes causing blisters and skin detachment. TEN and SJS are on the same spectrum of diseases; however, their difference comes from the disease severity, and they are classified based on the percentage of skin detachment.2

According to the classification of SJS/TEN:2

  • SJS has skin detachment less than 10%
  • SJS/TEN overlaps has skin detachment between 10-30%
  • TEN has skin detachment are more than 30%

According to most studies, TEN affects Asian and black patients more compared to the white population, and it affects assigned females at birth more than assigned males. Although it can affect any age group, the most affected age group is the patients between 50 and 70.1

Although TEN is a rare condition, it is associated with high mortality rates of up to 40%. That means every 4 patients out of 10 with TEN might not survive due to the condition.3 

Considering the high mortality, patients with TEN should be correctly diagnosed and should be started on the proper treatment without any delay.2

Causes of TEN

TEN can be triggered by many factors; however, a reaction to certain drugs is the most common cause. Sulfonamides and penicillins are the most common drug-induced causes, and herpes simplex virus is the most common infectious agent to cause TEN. 

While infections are the most common cause of TEN in children, drugs and cancers are more commonly the reason for TEN in adult patients.4 Possible causes of TEN include the following:1

  • Medications– Antibiotics (sulfonamides, chloramphenicol, penicillins, and quinolones), epilepsy medications (barbiturate, carbamazepine, phenytoin, valproate, and lamotrigine), some painkillers such as non-steroidal anti-inflammatory drugs (NSAID), especially oxybutazone and piroxicam, antiviral drugs (oseltamivir and abacavir), and allopurinol
  • Infections–Mycoplasma pneumoniae, hepatitis A and human herpes simplex virus
  • Cancers– Liver cancer, lung cancer
  • Vaccinations– Meningococcal vaccine

Although there might be several triggers of TEN, no defined cause is found in 25 to 50% of cases.4 According to recent studies, COVID-19-19 virus or the medications used for the infection might be the reason behind TEN cases reported in COVID-19 patients.1

There is increasing evidence regarding the genetic factor's contribution to the possibility of having TEN as an adverse reaction to a certain medication.2 

TEN: How does it develop? 

The immune system plays a role in the process leading to TEN. Previous studies suggested that certain proteins initiate the programmed death of the skin cells called keratinocytes. However, oxidative stress caused by reactive oxygen species can also be the facilitator for programmed cell death, also known as apoptosis.  

Programmed death of the keratinocytes results in damage to all layers of the epidermis, which is the outer part of the skin tissue. Full-thickness damage to the epidermis is the reason for the detachment from the underlying skin layer called the dermis.1

Clinical presentation

Symptoms usually start within 4 to 28 days following the exposure.  Early symptoms are usually mild and last up to 1 week. Early symptoms are also called prodromal symptoms and they include:4

  • Fever
  • Fatigue
  • Sore throat
  • Cough
  • Eye burning
  • Muscle ache
  • Joint pain

Following the prodromal symptoms, a measles-like rash and target lesions resembling a bull’s eye might appear. The rash begins on the upper body and spreads to other parts of the body, usually sparing palms and soles. As the disease progresses, lesions become purplish, and epidermal detachment occurs, which results in blister formation and subsequent painful scalding of the dead skin. 

TEN might affect mucosa, and it can lead to the involvement of the eyes, mouth, genitals, throat, respiratory system, and digestive system.4

Depending on the mucosal involvement, symptoms such as difficulty swallowing, pain when peeing, painful eyes, vision problems, and pain looking at bright lights can be seen.


TEN is diagnosed based on the history, clinical presentations, and skin biopsy. As most of the TEN cases are drug-related, detailed medical history plays a crucial role in diagnosis. 

On physical examination, your doctor might examine the lesions to check for a sign called the Nikolsky sign. Slight pressure application on the epidermis causes sloughing of the epidermis from the underlying skin. This is called a positive Nikolsky sign; however, it is not specific to TEN as it can be observed in other exfoliative skin conditions. Investigations for TEN include:

  • Skin biopsy: This is done by taking a piece of the affected skin to be examined in the laboratory. Immunofluorescent analysis is necessary to make a differential diagnosis during histopathological analysis of the skin biopsy. 
  • Blood tests: Although no specific blood tests exist to diagnose TEN, blood tests such as complete blood count, erythrocyte sedimentation rate, coagulation studies, urea and electrolytes, and liver function are necessary for management and follow-ups. 
  • Imaging studies: These are usually required in case of a complication such as lung involvement. Patch test– In around 50% of the patients, the patch test might help detect the cause leading to TEN.1 

Treatment and management

The crucial steps of the treatment are the early recognition of TEN and immediate cessation of the triggering agents. If these steps are taken within 24 hours of blister formation, they improve the outcome. 

Suspected TEN cases should be referred to a burn unit or intensive care unit, where they can receive specialised care.1 Supportive therapy is also important in the management of TEN. Supportive care measures involve:1

  • Airway management 
  • Fluid and electrolyte replacement
  • Pain management
  • Nutritional support
  • Wound care

Although there is no evidence regarding an effective pharmacological therapy for TEN, certain medications used in the treatment include:1

A recent study suggests that systemic steroids and cyclosporine are effective for TEN and SJS; however, no beneficial findings found for other pharmacotherapies.5


 Potential complications of TEN include:

  • Skin infections
  • Scarring of skin
  • Change in skin colour
  • Difficulty breathing
  • Eye problems such as sight problems, dry eyes, eye infections
  • Complications caused by scarring of  of the vagina and penis Involvement of liver and kidney

Skin infections are common and might cause serious consequences, such as sepsis and even death. Therefore, proper wound care is crucial for preventing skin infections. Breathing problems, clot formation in the lungs, kidney and heart failure, and bleeding from the digestive system are among the deadly complications of TEN.

Depending on the clinical presentation, complications should be managed with the expertise and input from other specialities. Psychological support following the discharge is also very important in the management of TEN.1

Factors influencing outcome SCORTEN (The severity-of-illness score for toxic epidermal necrolysis) is the most commonly used tool to predict the outcome of TEN patients. According to SCORTEN, factors worsening the outcome of TEN include the following:3

  • Age (>40 years)
  • Increased heart rate
  • Body surface area (>10%)
  • Increased serum urea
  • Decreased serum bicarbonate
  • Increased blood sugar
  • Cancer


Education regarding the causative agent is crucial to prevent future use of the medication. There is a possibility of cross-reactivity to the medications from the same class. Therefore, it is important to increase your knowledge regarding the causative agent as well as the potential risks and symptoms of TEN.

Awareness of TEN among healthcare professionals is also important to provide the best management. Early transfer to a burn unit or intensive care unit with a specialised team improves the outcome of the disease.1


What is the most common cause of toxic epidermal necrolysis?

The most common cause of TEN is adverse reactions to certain medications, particularly antibiotics, anticonvulsants, and painkillers.

Where does toxic epidermal necrolysis start?

TEN typically starts with flu-like symptoms such as fever and sore throat, followed by the appearance of a rash. The rash usually begins on the upper body and spreads to other parts of the body.

What does toxic epidermal necrolysis look like?

TEN presents as widespread blistering and skin detachment, resembling severe burns. It often leads to painful, large, and open sores on the skin.

Is toxic epidermal necrolysis contagious?

TEN is not contagious. It does not spread from person to person through touch or any other means.

What are the long-term effects of toxic epidermal necrolysis?

The long-term effects of TEN can include scarring, changes in skin colour, and potential complications such as breathing difficulties, eye problems, and infections. Psychological support is essential for patients dealing with its aftermath.


Toxic epidermal necrolysis is a severe, life-threatening skin condition causing skin detachment, often triggered by medications or infections. TEN and Stevens-Johnson syndrome (SJS) are related, differing in severity. Early symptoms include fever and rash, progressing to painful skin blistering and mucosal involvement.

Diagnosis involves medical history, physical examination, and skin biopsy.

Prompt recognition, stopping triggering agents, and specialized care are crucial. Complications, including skin infections and organ involvement, can be fatal. Prevention through medication awareness and educating healthcare professionals is essential for public safety.


  1. Labib A, Milroy C. Toxic epidermal necrolysis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Oct 9]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK574530/
  2. Hasegawa A, Abe R. Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Res [Internet]. 2020 Jun 16 [cited 2023 Oct 9];9:F1000 Faculty Rev-612. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308994/
  3. Lehloenya RJ. Disease severity and status in Stevens–Johnson syndrome and toxic epidermal necrolysis: Key knowledge gaps and research needs. Front Med (Lausanne) [Internet]. 2022 Sep 12 [cited 2023 Oct 9];9:901401. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510751/
  4. Wong A, Malvestiti AA, Hafner MDFS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review. Rev Assoc Med Bras [Internet]. 2016 Aug [cited 2023 Oct 9];62(5):468–73. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-42302016000500468&lng=en&tlng=en
  5. Fan WY, Zhai QR, Ma QB, Ge HX. Toxic epidermal necrolysis with systemic lupus erythematosus: case report and review of the literature. Annals of Palliative Medicine [Internet]. 2022 Jun [cited 2023 Oct 9];11(6):2144151–2142151. Available from: https://apm.amegroups.org/article/view/76782
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Ezgi Uslu Icli

Medical Doctor - Gazi University Medical School, Turkey

Ezgi has completed her studies in Medicine in 2017. After graduation, she worked as an emergency doctor followed by work experience as a research assistant in public health as well as undersea and hyperbaric medicine. She worked actively in the frontline during the COVID-19 pandemic as well.
She is passionate about medical writing as it helps increase health literacy and awareness of the public.
She moved to the UK in 2022 and she works as a volunteer in one of the NPOs for children in need.

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