Toxic epidermal necrolysis


Similar findings as Steven-Johnson syndrome with a greater degree of skin involvement.

Skin biopsy shows epidermal necrosis and detachment from the underlying dermis.

Incidence equal in males and females.

Mortality approximately 30%.

Toxic epidermal necrolysis

Toxic epidermal necrolysis a type of severe skin reaction.

With Stevens–Johnson syndrome it forms a spectrum of skin disease, with TEN being more severe.

Together with Stevens–Johnson syndrome, affects 1 to 2 persons per million per year.

It is more common in females.

Typical onset is over the age of 40.

Patients experience fever and flu-like symptoms, early.

Patients often have a flu-like prodrome, with a cough, runny nose, fever, decreased appetite and malaise.

A few days later the skin begins to blister and peel forming painful raw areas.

TEN results in extensive skin involvement with redness, necrosis, and detachment of the epidermal layer of the skin and mucosa.

Initial skin findings include red-purple, dusky, flat macules that start on the trunk and spread out from there.

Skin lesions transform into large blisters.

The affected skin can peel off in great swaths.

Mucous membranes, such as the mouth, are also typically involved as well.

A serious illness with complications that include: dehydration, sepsis, pneumonia, and multiple organ failure.

The mortality for toxic epidermal necrolysis is 25–30%.

Symptoms include: Fever, skin blisters, skin peeling, painful skin, and red eyes

Risk factors: systemic lupus erythematosus, genetic predisposition, HIV/AIDS.

HIV-positive individuals have 1000 times the risk of developing TEN compared to the general population.

TEN has also been reported to result from infection with Mycoplasma pneumoniae, dengue virus.

Contrast agents used in imaging studies as well as transplantation of bone marrow or organs have also been linked to TEN development.

Immune cytotoxic CD8+ T cells are primarily responsible for keratinocyte death and subsequent skin detachment.

Keratinocytes of the lower epidermis specialize in holding the surrounding skin cells together.

Differential diagnosis: Chickenpox, staphylococcal epidermolysis, staphylococcal scalded skin syndrome, autoimmune bullous disease.

Frequency 1–2 per million per year, together with Stevens-Johnson syndrome.

The most common cause are medications:lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics, and nevirapine.

TEN is caused 80–95% of the time by drug reactions.

The drugs most often implicated in TEN are:



beta-lactams (cephalosporins, penicillins, carbapenems)

nonsteroidal anti-inflammatory drugs


antimetabolites (methotrexate)

antiretroviral drugs (nevirapine)



anticonvulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine, and valproic acid).

Certain genetic factors are associated with increased risk of TEN: HLA-types such as, HLA-B*1502,[14] HLA-A*3101,[15] and HLA-B*5801 have been seen to be linked with TEN development when exposed to specific drugs.

A history of drug exposure exists on average 14 days prior to the onset of symptoms.

A history of drug exposure prior to symptoms ranges from 1–4 weeks.

TEN may result as early as 48 hours after drug exposure, if it is a reexposure.

Other causes can include infections such as Mycoplasma pneumoniae and cytomegalovirus.

Its cause may remain elusive.

Diagnosis is based on a skin biopsy and involvement of more than 30% of the skin.

A drug reaction with eosinophilia and systemic symptoms.

It is called Steven-Johnson syndrome when less than 10% of the skin is involved and an intermediate form with 10 to 30% involvement.

Mortality 20–50%.

Treatment typically takes place in a burn unit or intensive care unit.

Management includes: stopping the cause of TEN, pain medication, antihistamines, and antibiotics, intravenous immunoglobulins, and corticosteroids may also be used.

The course of the disease does not usually change with treatment.

The skin usually regrows over two to three weeks.

Recovery can take months.

Most patients have chronic problems.

Nearly all people with TEN have oral, eye and genital involvement.

The mouth can become blistered and eroded, making eating difficult.

The eyes can become swollen, crusted, and ulcerated, leading to potential blindness.

The most common problem with the eyes is severe conjunctivitis.

Complications for survivors include skin and eye damages:

Chronic skin manifestations can include scarring, eruptive melanocytic nevi, vulvovaginal stenosis, and dyspareunia.

Tracheal, bronchial, and G.I. tract epithelium may be involved.

Ocular symptoms are the most common complication in TEN, and can include dry eyes, photophobia, corneal scarring or xerosis, subconjunctival fibrosis, trichiasis, decreased visual acuity, and blindness.

It is suspected CD8+ immune cells become overactive by stimulation from drugs or drug metabolites, and then mediate keratinocyte cell death through release of a number of molecules, including perforin, granzyme B, granulysin tumor necrosis factor alpha and fas ligand.

Diagnosis is based on both clinical and histologic findings.

The presence of oral, ocular, and/or genital mucositis is helpful diagnostically, as these findings are present in nearly all patients with TEN.

The Nikolsky sign indicates the separation of the papillary dermis from the basal layer upon gentle lateral pressure.

The Asboe-Hansen sign is a lateral extension of bullae with pressure is also helpful diagnostic signs found in patients with TEN.

Definitive diagnosis of TEN often requires biopsy confirmation.

Prompt treatment improves outcome.

Definitive diagnosis of TEN often requires biopsy confirmation, showing necrotic keratinocytes.

With advanced TEN, full thickness epidermal necrosis is seen, with a subepidermal split, and scant inflammatory infiltrate in the papillary dermis.

Differential diagnosis:

Staphylococcal scalded skin syndrome

Drug-induced linear immunoglobulin A dermatosis

Acute graft versus host disease

Acute generalized exanthematous pustulosis


Drug reaction with eosinophilia and systemic symptoms

A generalized morbilliform eruption.

The primary treatment is discontinuation of the contributing/causative factor(s).

Management in ICU’s, supportive care and nutritional support.

Trials are needed to assess the benefit of IVIG in TEN.

The earlier a causative medication is withdrawn the better the prognosis.

The leading cause of death is infections by fungi and bacteria, due to loss of protective skin.

Death is caused by respiratory distress which is either due to pneumonia or damage to the linings of the airway.

Severity of Illness Score for Toxic Epidermal Necrolysis:one point for each factor

age >40

heart rate >120 beats/minute

diagnosis of cancer

separation of epidermis on more than ten percent of body surface area (BSA) on day 1.

Blood Urea Nitrogen >28 mg/dL

Glucose >252 mg/dL

Bicarbonate <20mEq/L


0–1: 3.2% mortality

2: 12.2% mortality

3: 35.3% mortality

4: 58.3% mortality

≥5: 90% mortality

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