Toxic Epidermal Necrolysis

TEN, TEN syndrome, Lyell syndrome, Lyell’s syndrome

Toxic epidermal necrolysis is a rare but extremely serious skin condition that causes large areas of skin to blister and peel away, leaving raw, painful wounds that resemble severe burns. This life-threatening reaction is usually triggered by certain medications and affects at least 30% of the body’s surface, including sensitive areas like the mouth, eyes, and genitals.

Table of contents

• What is toxic epidermal necrolysis?
• What causes this condition?
• Who is at risk?
• Signs and symptoms
• Serious complications
• How doctors diagnose TEN
• Treatment and hospital care
• What to expect and survival rates

What is toxic epidermal necrolysis?

Toxic epidermal necrolysis (TEN) is a painful, life-threatening skin condition that causes large areas of blistering and peeling skin on at least 30% of the body, including mucous membranes (moist linings of body openings) like the mouth, eyes, and genitals.^[1] The condition was first described by Alan Lyell in 1956 as “an eruption resembling scalding of the skin.”^[3]

TEN is the most severe form of a group of related skin conditions. Stevens-Johnson syndrome (SJS) is a milder form of the same disease process. The main difference between them is how much of the body’s surface is affected. SJS involves less than 10% of the body surface, while TEN affects more than 30%. When the condition involves 10% to 30% of the body, doctors call it an overlap between the two conditions.^[1]

The widespread damage to the skin can lead to dangerous fluid loss and serious infections. This is a medical emergency that requires immediate hospital treatment.^[2]

What causes this condition?

In most cases, experts believe that certain medications trigger TEN. The body develops an abnormal immune reaction to these drugs, causing skin cells to die and the outer layer of skin to separate from the layer underneath.^[3] Symptoms typically appear one to four weeks after starting a new medication, though they can develop as early as 48 hours if someone takes a drug they’ve reacted to before.^[5]

The medications most commonly linked to TEN include:^[1][3]

• Allopurinol (a drug used to treat kidney stones and gout)
• Anticonvulsants (drugs used to treat seizures), including lamotrigine, carbamazepine, phenytoin, phenobarbital, and valproate
• Sulfonamide antibiotics (sulfa drugs), including sulfamethoxazole and sulfasalazine
• Other antibiotics, such as penicillins and quinolones
• Anti-retroviral drugs used to treat HIV, especially nevirapine, efavirenz, and etravirine
• Certain pain medications called oxicam-NSAIDs (nonsteroidal anti-inflammatory drugs), such as piroxicam and meloxicam

Less commonly, TEN can be triggered by:^[1][3]

• Infections, such as Mycoplasma pneumoniae, hepatitis A, or human herpesvirus 7
• Vaccinations, especially meningococcal vaccine
• Certain cancers, such as hepatocellular carcinoma and lung cancer

In some cases, doctors cannot identify what caused the condition.^[1]

Who is at risk?

Toxic epidermal necrolysis is rare, affecting about 1 to 2 people per million each year.^[4][3] People of any age can develop TEN, though it is more common in older adults.^[1]

Certain factors increase the risk of developing this condition:^[1][4]

• Having a weakened immune system from conditions like HIV/AIDS or lymphoma
• Having systemic lupus erythematosus (a chronic inflammatory disease)
• Genetic factors—some people cannot normally break down certain medications, which makes their body more likely to react badly. Certain gene variations may make individuals or ethnic groups more likely to react to particular drugs
• Having had TEN or Stevens-Johnson syndrome before—taking the same drug or similar drugs again increases the risk of another reaction

Signs and symptoms

TEN typically begins with flu-like symptoms that last for one to three days before the skin problems appear. These early symptoms include:^[1][2]

• Fever and chills
• Body aches
• Cough
• Headache
• Sore throat
• Redness and inflammation in the eyes
• Decreased appetite and general feeling of being unwell

A few days later, a painful skin rash develops. The rash usually starts on the face and chest before spreading rapidly to other parts of the body, including the arms, legs, and genitals.^[1][6] The rash may appear as circular patches that are darker in the middle and lighter around the outside.^[6]

The skin then begins to blister and peel in large sheets, forming very painful raw areas called erosions (open wounds) that look like severe burns.^[2] The skin often peels very easily when touched.^[6]

Blisters and sores also develop on mucous membranes, including:^[1]

• Inside the mouth, throat, and nose—making swallowing painful
• In the eyes, affecting the conjunctiva (inside of the eyelid) and cornea (clear front covering of the eye)—causing eye pain and sensitivity to light
• In the airways—which can make breathing difficult
• In the urinary tract and genitals—causing pain when urinating
• Around the anus

The condition progresses rapidly, often within three days of the first skin symptoms appearing.^[3]

Serious complications

Because the skin normally acts as a protective barrier, extensive skin damage can lead to life-threatening problems. Complications of TEN include:^[1][2]

• Dangerous loss of fluids and salts from the body (dehydration)
• Serious bacterial infections that spread through the bloodstream (sepsis)
• Pneumonia
• Multiple organ failure
• Shock

Long-term problems in survivors can include changes in skin color, dryness of the skin and mucous membranes, excessive sweating, hair loss, and abnormal growth or loss of fingernails and toenails. Some people develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light and vision problems. Other lasting issues may include impaired taste, difficulty urinating, and genital abnormalities.^[4][5]

How doctors diagnose TEN

Doctors can usually diagnose TEN by examining the skin and listening to a description of symptoms. They will ask about any medications the person has taken recently.^[1][2]

To confirm the diagnosis, doctors may perform a skin biopsy—removing a tiny sample of skin to examine under a microscope. The biopsy shows dead skin cells and detachment of the outer layer of skin (epidermis) from the layer underneath (dermis).^[1]

Other tests may include blood tests and cultures of blood, skin, and mucous membranes to check for infection.^[3]

Treatment and hospital care

TEN requires immediate treatment in a hospital, often in a burn unit or intensive care unit.^[2][10] Early transfer to specialized care has been shown to reduce the risk of infection, lower the death rate, and shorten hospital stays.^[7]

The most important first step is to stop the medication causing the reaction as quickly as possible. Studies show that stopping the drug early can significantly improve survival.^[10]

The main treatment is supportive care to keep the patient comfortable and safe while the skin heals. This includes:^[6][11]

• Fluid replacement—giving fluids and salts through a vein to prevent dehydration. Patients typically need less aggressive fluid replacement than burn patients because the blood vessels are less damaged
• Wound care—gently cleaning the affected skin and applying protective dressings infused with petroleum jelly or medication
• Pain management—providing strong pain medications to help ease discomfort. Mouthwash containing a numbing agent like lidocaine may be used for mouth pain
• Infection prevention and treatment—monitoring for signs of infection and giving antibiotics when needed. Isolation may be used to prevent infection
• Nutritional support—providing food through a tube inserted through the nose into the stomach if needed
• Breathing assistance—monitoring the airways and providing breathing support if needed, including mechanical ventilation in severe cases
• Eye care—applying preservative-free artificial tears and potentially corticosteroid eye drops to control inflammation. An eye specialist (ophthalmologist) should examine the patient

Additional treatments that may be used include:^[10][11]

• Intravenous immunoglobulin G
• Corticosteroids
• Other medications that affect the immune system, such as cyclosporine

Recovery can take several weeks to months. The skin usually regrows over two to three weeks, but full recovery can take much longer, and most people are left with some chronic problems.^[5]

What to expect and survival rates

Toxic epidermal necrolysis is a life-threatening condition. About 20% to 50% of people with TEN do not survive, with the typical death rate being around 25% to 30%.^[1][3][5]

The chance of survival depends on several factors, including how quickly treatment begins, how much of the body is affected, the person’s age, and whether they have other health conditions. Older patients and those with more extensive skin involvement face higher risks.^[5]

Anyone who survives TEN must permanently avoid the medication that caused the reaction, as well as related drugs. Taking the same medicine again greatly increases the risk of another, potentially fatal reaction.^[2][6]

It’s likely that survivors will feel very tired for several weeks after leaving the hospital and may experience ongoing health issues related to the skin, eyes, or other affected areas.^[6]