Toxic Epidermal Necrolysis (TEN)

What happens in TEN

TEN is a delayed immune reaction. Immune cells (cytotoxic T cells and natural killer cells) recognize the drug and trigger widespread death of keratinocytes, the cells of the top skin layer, mainly through a protein called granulysin. The dead epidermis separates from the layer below, leaving raw, painful areas like a severe burn. Mucous membranes of the mouth, eyes, genitals and sometimes the airways and gut are also affected.

SJS vs TEN

See Stevens-Johnson syndrome for the milder end of the spectrum.

Causes

Medicines (most cases)

• allopurinol (gout)
• anti-seizure drugs: carbamazepine, lamotrigine (especially with rapid dose increase), phenytoin, phenobarbital
• sulfonamide antibiotics: trimethoprim-sulfamethoxazole
• nevirapine (HIV)
• oxicam NSAIDs (meloxicam, piroxicam)
• other antibiotics: some penicillins, cephalosporins, fluoroquinolones
• acetaminophen has been reported rarely

Other triggers

• Mycoplasma pneumoniae infection, especially in children (often with severe mucous membrane involvement)
• herpes simplex virus and other infections
• vaccines and immune checkpoint inhibitors, rarely

Genetic risk

Certain HLA gene types greatly increase risk with specific drugs, for example HLA-B*15:02 with carbamazepine in people of Southeast Asian ancestry, and HLA-B*58:01 with allopurinol. Testing is recommended before starting these drugs in at-risk groups.

Symptoms

Early (1 to 3 days before the rash)

• fever
• sore throat, cough, runny nose
• burning or red eyes
• body aches, feeling unwell

Skin and mucous membranes

• painful red or dusky purple spots, often starting on the face and trunk
• target-like lesions that merge
• blisters that break, leaving raw skin
• skin peeling in sheets; the skin slides off with gentle pressure (Nikolsky sign)
• painful mouth sores and crusted lips
• red, painful eyes with discharge
• genital and anal sores
• painful urination

Diagnosis

• clinical assessment of the rash and detached area
• skin biopsy confirms full-thickness skin cell death and rules out look-alikes such as staphylococcal scalded skin syndrome, which splits at a higher level
• medication history to identify the likely culprit drug (tools like the ALDEN algorithm help)
• SCORTEN score, using age, heart rate, cancer, skin detachment, and blood urea, glucose and bicarbonate, predicts mortality
• tests for Mycoplasma and other infections

Treatment

Immediate

• stop the suspected drug and any non-essential medicines
• admit to a burn unit or ICU experienced in SJS/TEN

Supportive care

• gentle skin care: non-adherent dressings, leaving detached skin in place as a biological dressing in some approaches
• warm environment, fluid and electrolyte replacement
• nutrition, often by feeding tube
• pain control
• infection prevention and monitoring; antibiotics only for confirmed infection
• eye care by an ophthalmologist daily to prevent scarring and blindness
• mouth care, urogenital care to prevent adhesions
• breathing support if airways are involved

Medicines

Evidence is limited. Options used in some centers include cyclosporine, etanercept, IV immunoglobulin and corticosteroids.

Complications

• sepsis and multi-organ failure
• eye scarring, chronic dry eye, vision loss
• skin color changes and scarring, nail and hair loss
• narrowing of the esophagus, urethra or vagina
• lung damage
• psychological effects, including PTSD

Outlook and prevention

Recovery of skin takes 2 to 3 weeks, but eye and other complications can be long-lasting. Survivors must never take the causative drug again, or closely related drugs, and should wear a medical alert bracelet. Family members may share genetic risk for the same drug.

Frequently asked questions

What causes toxic epidermal necrolysis?

Most cases are triggered by medicines, especially allopurinol, carbamazepine, lamotrigine, phenytoin, sulfa antibiotics and nevirapine. Infections such as Mycoplasma pneumoniae cause some cases, particularly in children. Certain genes increase the risk with specific drugs.

What are the first signs of TEN?

TEN often starts like the flu, with fever, sore throat and burning eyes, followed within days by a painful red or purple rash that spreads and blisters, with sores in the mouth, eyes and genitals. Anyone with these symptoms after a new medicine needs emergency care.

What is the difference between Stevens-Johnson syndrome and TEN?

They are the same disease at different severities. Stevens-Johnson syndrome involves less than 10% of the body surface, while TEN involves more than 30%. Between 10 and 30% is called SJS/TEN overlap. TEN is more dangerous.

Can you fully recover from TEN?

Many people survive and the skin regrows within weeks, but long-term problems are common, especially with the eyes, such as dryness and scarring. Ongoing eye, skin and psychological follow-up helps recovery.