Toxic Epidermal Necrolysis - Cause, Symptoms, Risk Factors, Diagnosis, and Treatment

What Is Toxic Epidermal Necrolysis?

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 percent 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, including controlling pain, dressing wounds, and electrolyte replacement. 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 more than 30 percent of the body surface area in TEN and < 10 percent of the body surface area in SJS; involvement of 10 to 30 percent of the body surface area is considered an overlap of SJS and TEN.

What Causes Toxic Epidermal Necrolysis?

Medications are the main etiology for over 50 percent of SJS cases and up to 95 percent 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).

• 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?

• Prodrome Development: Patients experience a prodrome characterized by cough, fever, headache, malaise, and keratoconjunctivitis within the initial one to three weeks after drug administration, increasing the risk of Toxic Epidermal Necrolysis (TEN).

• Initial Skin Abnormality: The first noticeable abnormality is diffuse erythema of the skin, serving as an early indicator of potential TEN development.

• Target Configuration Macules: Macules suddenly manifest in a target configuration, typically appearing on the face, neck, upper trunk, and vagina.

• Coalescence into Bullae: Over time, these macules coalesce into large, flaccid bullae, creating a significant clinical feature.

• Epithelial Sloughing: Extensive sloughing of epithelial tissues occurs, involving not only the skin but also the nails, eyebrows, palms, and soles, contributing to the severity of the condition.

• Painful Manifestations: Patients commonly experience pain affecting the skin, mucosa, and eyes, adding to the overall discomfort associated with the condition.

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: Certain genetic variations increase the risk of the disease.

• Patients With a Weak Immune System: The immune system can be affected by autoimmune diseases, Human Immunodeficiency Virus (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 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 percent of cases. When the bronchial epithelium shows sloughing, there is a cough, dyspnea, pneumonia, pulmonary edema, and hypoxemia. Glomerulonephritis and hepatitis may develop as well.

What Are the Treatment and Management for Toxic Epidermal Necrolysis?

Treatment of the condition works 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.

• Patients highly susceptible to infections 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 two to three 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 using TNF-alpha inhibitors– Infliximab and Etanercept.

Management of Toxic Epidermal Necrolysis includes the following:

The management of Toxic Epidermal Necrolysis (TEN) includes:

• Immediate Hospitalization: Swift admission to a specialized unit for close monitoring.

• Discontinuation of Causative Medications: Stop the medications causing TEN to prevent symptom escalation.

• Supportive Care: Provide a sterile environment, proper wound care, and prevent dehydration.

• Nutritional Support: Offer parenteral or enteral nutrition to meet metabolic needs.

• Pain Management: Prioritize effective pain relief.

• Psychosocial Support: Offer assistance to the patient, including counseling and additional support as necessary.

• Ophthalmologic Consultation: Address specific symptoms and prevent ocular complications.

• Long-Term Follow-Up: Ensure ongoing monitoring for potential ocular and psychological complications.

What Is the Prognosis for Toxic Epidermal Necrolysis?

Severe cases are similar to extensive burns. It can be considered 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 percent. The severity of Toxic Epidermal Necrolysis (TEN) is assessed through a scoring system, indicating mortality rates based on risk factors within the first 24 hours:

• 0–1 Score: 3.2% Mortality Rate (CI: 0.1 to 16.7)

• 2 Score: 12.1% Mortality Rate (CI: 5.4 to 22.5)

• 3 Score: 35.3% Mortality Rate (CI: 19.8 to 53.5)

• 4 Score: 58.3% Mortality Rate (CI: 36.6 to 77.9)

• ≥ 5 Score: >90% Mortality Rate (CI: 55.5 to 99.8)

CI - Confidence Interval: A confidence interval is a statistical way of expressing that the range within the calculated value (an average or percentage) is likely to fall.

What Are The Long-Term Effects of Toxic Epidermal Necrolysis?

Toxic Epidermal Necrolysis (TEN) can have enduring effects, including:

• Skin Scarring: Long-lasting skin scarring is common due to damage during the acute phase, impacting both appearance and function.

• Ocular Complications: Involvement of the eyes can result in chronic dry eyes, light sensitivity (photophobia), and vision issues.

• Psychological Impact: The trauma of TEN can lead to persistent psychological effects, including anxiety, Post-Traumatic Stress Disorder (PTSD), and depression.

• Medication Sensitivities: Individuals may develop sensitivities to certain medications and need to avoid specific drugs to prevent recurrence.

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 healthcare providers about the history of toxic epidermal necrolysis and carrying a medical 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.