Toxic Epidermal Necrolysis (TEN): Causes, Symptoms, Treatment, and Survival Rate

Toxic epidermal necrolysis (TEN) is a rare, life-threatening skin reaction. It is most commonly triggered by certain medications. However, in rare cases, it can be caused by infections or vaccinations. 

A severe form of Steven-Johnson’s syndrome (SJS), TEN is diagnosed when you have large areas of blistering and peeling skin on more than 30% of your body. TEN also causes extensive damage to the moist linings (mucous membranes) in the mouth, nose, throat, eyes, and genitals.
In SJS, you have small areas of peeling skin, affecting less than 10% of your body. SJS-TEN overlap disease is when 10% to 30% of the body is affected.  

How Common Is Toxic Epidermal Necrolysis?

TEN is a rare condition, affecting 1.9 people per million U.S. adults each year [1]. 

What Causes Toxic Epidermal Necrolysis?

In some cases, the exact cause is not known. In others, several factors can induce TEN, including:

• Antiseizure medications: Phenobarbital, phenytoin, carbamazepine, valproic acid, and lamotrigine
• Antibacterial drugs: Sulfonamides (trimethoprim-sulfamethoxazole), chloramphenicol, penicillins, and ciprofloxacin
• Non-steroidal anti-inflammatory drugs (NSAIDs): Piroxicam, meloxicam
• Antigout agents: Allopurinol
• Anti-HIV medications: Nevirapine and abacavir

Rare triggers can include:

• Bacterial infections: Mycoplasma pneumoniae infections
• Viral infections: Herpes and hepatitis A
• Vaccines: Meningococcal B and MMR vaccines 
• Graft-versus-host disease  

Risk Factors

The following factors can increase your risk of TEN:

• HIV infection 
• Weak immune system (such as in HIV/AIDS and autoimmune disorders)
• Personal or family history of TEN
• Genetic factors
• Cancer (specifically blood cancers)

Symptoms

Symptoms may appear a few weeks after you start taking a drug. Initially, you may have flu-like symptoms, such as:

• Body aches
• Cough 
• Fever 
• Chills
• Headache
• Red and swollen eyes

As the disease progresses, you may have:

• Widespread skin pain
• A rapidly spreading rash affecting more than 30% of your body
• Blisters and peeling skin 
• Sores and swelling on the mucous membranes, including the mouth, eyes, respiratory tract, and genitals

These signs and symptoms may resemble other skin diseases. Because TEN is life-threatening, seek immediate medical care if you think you have symptoms of TEN. 

Toxic Epidermal Necrolysis Treatment

People with TEN need emergency care at a hospital, preferably in an intensive care unit (ICU) or burn center. Treatment is mainly supportive and includes [2]:

• Stopping all potential triggers
• Isolation to prevent infection
• Administering IV fluids and nutrition
• Protective dressings and antibacterial creams or ointments to prevent skin infection
• Antibiotic therapy if signs of infection are present
• Medications to reduce pain
• Eye and oral cavity examination 
• Oxygen via a face mask (if needed)
• Medications to prevent blood clots

No specific treatment for TEN exists. However, your provider may consider the following based on your age, symptom severity, expectations, and preferences:

Intravenous Immunoglobulin (IVIG)

IVIG is a sterile liquid that contains disease-fighting proteins (immunoglobulins or antibodies). Some studies show that early treatment with high-dose IVIG can improve survival and speed recovery [3].

Systemic steroids

Your provider may give you a steroid to halt the progression of TEN. Nonetheless, the use of steroids is highly controversial. Some studies suggest that steroids may increase the risk of death. 

IVIG With Steroids

According to a recent review published in the Journal of the American Academy of Dermatology, clinicians should consider combination therapy with IVIG and steroids to treat TEN [4]. The authors of the review conclude that this combination may reduce death risk in individuals with TEN. 

Plasmapheresis (Plasma Exchange)

Plasmapheresis separates the liquid part of the blood (plasma) from blood cells. Following separation, the blood cells are mixed with a liquid and infused back into the body. 
Daily plasmapheresis for 3 days can help remove the causative drug, its byproducts, and other inflammatory substances from the body. 

Tumor Necrosis Factor-Alpha (TNF-Alpha) Inhibitors

TNF-alpha inhibitors, such as infliximab and etanercept, may help resolve skin lesions in toxic epidermal necrolysis. They may be used alone or as a second-line medication.  

Toxic Epidermal Necrolysis Survival Rate

Toxic epidermal necrolysis causes death in about 25% of the cases, and the death rate is lower in children (less than 10%). The death rate is higher if you [5, 6]:

• Are over 40 
• Have high blood sugar
• Have a fast heart rate
• Have chronic kidney disease

Complications

People older than 70 years are most likely to develop complications. Likewise, the risk of complications is higher in people with liver cirrhosis (scarring of the liver) or cancer. 
Complications of TEN include:

Sepsis

Sepsis or blood infection is a life-threatening condition. It happens when the immune response to an infection damages your body’s vital organs, putting you into shock and causing organ failure. 

Breathing Problems

If your lungs are involved, you may find it difficult to breathe. In severe cases, your lungs may be too weak, causing an excess of carbon dioxide and a deficiency of oxygen in your blood. 

Eye Problems

Eye problems associated with TEN are dry eye, ingrown eyelashes, corneal scarring, and, in rare cases, blindness.
 

Toxic Epidermal Necrolysis Long-Term Effects

Some long-term effects among TEN survivors are:

• Dry itchy skin
• Hair or nail loss
• Excessive sweating
• Dry eyes
• Sensitivity to light 
• Dry mouth
• Lung damage

In a recent survey of 121 TEN/SJS survivors, more than half screened positive for depression, and over 40% screened positive for anxiety [7].
 

Toxic Epidermal Necrolysis (TEN) vs Steven-Johnson’s Syndrome (SJS)

The major differences between TEN and SJS are as follows:

Frequently Asked Questions

Which drug causes toxic epidermal necrolysis?

Medications commonly associated with toxic epidermal necrolysis are:

• Antiseizure medications: Phenobarbital, phenytoin, carbamazepine, valproic acid, and lamotrigine
• Antibacterial drugs: Sulfonamides (trimethoprim-sulfamethoxazole), chloramphenicol,  penicillins, and ciprofloxacin

What causes epidermal necrolysis?

Medications are the primary causes of TEN in adults, whereas infections are the main causes in children.  

Which layer of skin is affected by toxic epidermal necrolysis?

Toxic epidermal necrolysis causes the top layer of your skin (epidermis) to detach from the lower layers of skin (dermis). 

What are the clinical features of toxic epidermal necrolysis?

TEN causes peeling skin on more than 30% of your body. It also causes extensive damage to the moist linings (mucous membranes) in the mouth, nose, throat, eyes, and genitals.