When Stevens-Johnson syndrome (SJS) presents with severe manifestations, it is referred to as toxic epidermal necrolysis (TEN). It is a rare, life-threatening reaction of the skin. It is diagnosed when there are large areas of blistering and peeling of skin on at least 30 % of the body, causing extensive damage to the mucous membranes (the moist linings) of the eyes, mouth, and genitals. The widespread skin damage can lead to excessive loss of body fluids and may predispose to infections. It affects people of all age groups. Toxic epidermal necrolysis usually requires hospitalization, and recovery may take weeks to months. As the skin heals, supportive care is required for the patients, and this includes controlling pain, dressing the wounds, and electrolyte replacement for the patient. If the etiology of the disease was due to a medication, the particular drug must be avoided permanently.

Toxic Epidermal Necrolysis Versus Steven Johnson Syndrome

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are similar in clinical presentation but vary in the extent of distribution. The dermal changes affect > 30 % of body surface area in TEN and < 10 % of body surface area in SJS; involvement of 10 % to 30 % of body surface area is considered as an overlap of SJS and TEN.

What Causes Toxic Epidermal Necrolysis?

Medications are the main etiology for over 50 % of SJS cases and up to 95 % of TEN cases. The most common drug causes include,

The sulfa group of drugs (e.g., Cotrimoxazole, Sulfasalazine).
Other antibiotics (e.g., Aminopenicillins, Fluoroquinolones, Cephalosporins).
Non-steroidal anti-inflammatory drugs (e.g., Piroxicam, Meloxicam).
Antiretroviral drugs (e.g., Nevirapine).
Antiseizure drugs (e.g., Phenytoin, Phenobarbital, Carbamazepine, Lamotrigine, Valproate).
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Other miscellaneous drugs (e.g., Allopurinol, Chlormezanone).

Non-drug-related cases include,

Infection (mostly with Mycoplasma pneumoniae).
Graft-vs-host disease.
Vaccination.

In certain cases, the cause may not be identified.

What Are the Symptoms of Toxic Epidermal Necrolysis?

Patients develop a prodrome of cough, fever, headache, malaise, and keratoconjunctivitis within the initial one to three weeks after administration of the drug that predisposes them to TEN. The first abnormality to be noted usually is the diffuse erythema of the skin. Macules suddenly appear in a target configuration, usually on the face, neck, upper trunk, and vagina. These macules eventually coalesce into large flaccid bullae and slough over a period of one to three days. Loss of epithelium is noted, including those of the nails and eyebrows, palms, and soles. Pain involving the skin, mucosa, and eye are common.

What Are the Risk Factors for Toxic Epidermal Necrolysis?

A family history of Stevens-Johnson syndrome and toxic epidermal necrolysis. A person is more susceptible to the condition if a parent or a sibling has had it.
If a drug causes this condition, there is a risk of a recurrence if used again.
Genetic Factors: Having certain genetic variations puts you at increased risk of the disease.
Patients With a Weak Immune System: The immune system can be affected by autoimmune diseases, HIV or AIDS, and organ transplants.Among people with HIV, the incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis is about 100 times greater in HIV patients when compared to HIV-free individuals.
Cancer: People with cancer, especially cancers of the blood, are at increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis.

What Are the Manifestations In Severe Cases of In Toxic Epidermal Necrolysis?

In severe cases, patients exhibit the Nikolsky sign where layers of epithelium peel off the body at pressure points, exposing reddish and painful skin. Painful oral erosions, keratoconjunctivitis, and genital problems are seen, along with skin sloughing in about 90 % of cases. When the bronchial epithelium shows sloughing, there is cough, dyspnea, pneumonia, pulmonary edema, and hypoxemia. Glomerulonephritis and hepatitis may develop as well.

What Is the Treatment for Toxic Epidermal Necrolysis?

Treatment of the condition works the best when the diagnosis is made early. It is treated in an inpatient dermatologic or intensive care unit setting if it is mild to moderate and in a burn unit, if it is severe.
Potentially causative drugs should be stopped immediately.
As the patients are highly susceptible to infections, they are isolated to minimize exposure and are given fluids, electrolytes, blood products, and nutritional supplements as required.
Skincare includes daily wound care similar to severe burns and prompt treatment of secondary bacterial infections.
Cyclosporine has been shown to decrease the duration of active disease by 2 days to 3 days in some instances and possibly decrease mortality.
Plasmapheresis removes reactive drug metabolites or antibodies and can be considered.
The inflammation can be reduced by the use of TNF-alpha inhibitors– Infliximab and Etanercept.

What Is the Prognosis for Toxic Epidermal Necrolysis?

Severe cases are similar to extensive burns. It can be considered as an acute illness where the patient may be unable to eat or open the eyes and suffer massive fluid and electrolyte losses. They are more prone to infection, multiorgan failure, and death. If there is an early treatment intervention, survival rates are almost 90 %. There is a severity-of-illness score for toxic epidermal necrolysis, which systematically scores seven independent risk factors within the first 24 hours of hospitalization to determine the mortality rate for a patient and is presented as follows:

* More risk factors indicate a higher score and a higher mortality rate (%) as follows:

0–1 = 3.2 % (CI: 0.1 to 16.7)
2 = 12.1 % (CI: 5.4 to 22.5)
3 = 35.3 % (CI: 19.8 to 53.5)
4 = 58.3 % (CI: 36.6 to 77.9)
≥ 5 = > 90 % (CI: 55.5 to 99.8)

CI = confidence interval.

Conclusion:

Be aware of medicines that cause Stevens-Johnson syndrome and toxic epidermal necrolysis in the first place and avoid them to prevent another episode of TEN. Informing future health care providers about the history of Toxic Epidermal Necrolysis and carrying a medic alert bracelet with information about the condition will help avoid administering the drug by mistake. Recurrence of the condition could be worse and life-threatening.