Toxic epidermal necrolysis (TEN), also known as Lyell’s syndrome, is a rare but life-threatening dermatologic condition characterized by the widespread detachment of the epidermis. It is considered a more severe form of Steven-Johnson syndrome (SJS), both of which are typically caused by medications. TEN is distinguished from SJS primarily by the extent of skin involvement, with TEN involving more than 30% of the total body surface area (BSA). This condition can affect individuals of any age, but there is an increasing incidence with age. The pathophysiology, clinical presentation, diagnostic strategies, and management options for TEN are discussed below, emphasizing the critical aspects of treatment and prognosis.

Pathophysiology and Etiology

Toxic epidermal necrolysis is most often triggered by medications, with common culprits including allopurinol, anticonvulsants (e.g., phenytoin, carbamazepine), nonsteroidal anti-inflammatory drugs, and antibiotics (e.g., sulfonamides). In rare cases, TEN can also be induced by infections or immunizations. The pathogenesis of TEN involves a dysregulated immune response where drug metabolites bind to keratinocytes, triggering apoptosis and widespread epidermal cell death. This process results in the detachment of the epidermis from the dermis, leading to the characteristic blistering and sloughing of the skin.

Both TEN and SJS share similar immunologic mechanisms, with a significant role of cytotoxic T cells and natural killer cells, which contribute to keratinocyte apoptosis. However, TEN is distinguished by the greater extent of epidermal detachment and more severe mucosal involvement, which is indicative of its higher morbidity and mortality rates compared to SJS.

Clinical Presentation

TEN typically begins with a prodrome of flu-like symptoms, including fever, malaise, sore throat, and body aches, occurring 1–3 days before the development of characteristic mucocutaneous lesions. The skin manifestations often begin as poorly defined erythematous macules that rapidly evolve into blistering and large areas of epidermal sloughing. The lesions usually start on the face, trunk, and upper extremities before spreading to other areas. The mucosal surfaces, especially the mouth, eyes, and genitalia, are commonly affected and may develop painful erosions, which complicate the course of the disease.

As the disease progresses, extensive skin detachment leads to the appearance of large, sheet-like areas of epidermal loss, resembling severe burns. This extensive damage exposes the dermis, making the affected areas prone to fluid loss, infection, and other complications. The rapid progression of epidermal detachment is a hallmark of TEN, distinguishing it from other dermatologic conditions.

Complications

TEN is associated with a high risk of severe complications, primarily due to the loss of the epidermal barrier. These complications include:

• Dehydration and fluid imbalance: Extensive skin detachment leads to significant fluid loss, which can result in hypovolemia and shock.
• Infection: The loss of the skin barrier increases the risk of secondary bacterial, fungal, and viral infections. Sepsis is a major cause of morbidity and mortality in TEN patients.
• Nutritional deficiencies: Patients may experience difficulty eating or absorbing nutrients due to mucosal lesions, resulting in malnutrition.
• Ocular complications: Eye involvement can lead to blindness if not treated promptly, particularly if there is corneal involvement.
• Gastrointestinal hemorrhage: Mucosal erosion in the gastrointestinal tract can lead to bleeding and further complicate the disease course.
• Death: Due to the severity of the condition, mortality rates for TEN range from 25%-35%, depending on factors such as the extent of skin involvement, underlying health conditions, and the promptness of treatment.

Diagnosis

The diagnosis of TEN is primarily clinical, based on the characteristic signs and symptoms. The involvement of 30% or more of the total body surface area (BSA) by skin detachment is critical for the diagnosis of TEN, as defined by the SCORTEN score. This severity score is used to assess the prognosis based on factors such as age, underlying conditions, and the extent of skin involvement. The clinical examination of the skin and mucous membranes often provides sufficient evidence to initiate treatment. However, if there is any uncertainty in the early stages, a skin biopsy may be performed to confirm the diagnosis and rule out other potential causes of epidermal necrosis, such as viral infections or autoimmune diseases.

Management and Treatment

Management of TEN requires rapid identification and intervention to reduce mortality and morbidity. The first step in the treatment of suspected TEN is the immediate discontinuation of the offending drug. Early intervention is critical, as continued exposure to the causative agent can worsen the condition. Once the offending medication is stopped, supportive care is paramount.

• Supportive Therapy: Given the extensive epidermal loss, patients with TEN often require intensive supportive management, including fluid resuscitation, electrolyte balance correction, and pain management. Maintenance of body temperature is also critical to prevent hypothermia.
• Wound Care and Infection Prevention: Due to the risk of infection, wound care involves gentle cleaning of the skin and the application of appropriate dressings. Antiseptic solutions are used to prevent secondary bacterial infection, though prophylactic antibiotics are not recommended unless an infection is identified. If bacterial infection occurs, systemic antibiotics should be administered based on culture results.
• Referral to Intensive Care: Patients with severe TEN (involving more than 30% BSA) often require care in an intensive care unit or burn unit, where specialized wound care and monitoring are available. The SCORTEN score can guide decisions regarding the intensity of care required.
• Immunosuppressive Therapy: Although the use of systemic corticosteroids is controversial, some studies have suggested that early administration of corticosteroids, intravenous immunoglobulin, or cyclosporine may help reduce mortality in severe cases. However, their efficacy remains debated, and these treatments are typically reserved for refractory cases.
• Ocular Care: Ocular involvement in TEN can lead to permanent damage if not promptly managed. Frequent ocular examinations and the use of lubricating eye drops are essential to prevent corneal damage. Referral to an ophthalmologist for severe cases is recommended.

Prognosis

The prognosis of TEN is largely determined by the extent of skin involvement, age, and the presence of underlying health conditions such as HIV or cancer. The SCORTEN score is an important prognostic tool, with higher scores correlating with increased mortality. Early diagnosis and prompt removal of the causative agent, along with aggressive supportive care, can improve outcomes, but the condition remains highly fatal in severe cases.

Conclusion

Toxic epidermal necrolysis is a rare, severe, and potentially fatal condition characterized by extensive epidermal detachment. The condition most often arises as a reaction to certain medications and is distinguished from SJS by the extent of skin involvement. Early identification, prompt discontinuation of the causative agent, and comprehensive supportive care are critical to improving patient outcomes. Although the management of TEN remains complex, advances in treatment, including the use of immunomodulatory therapies, offer hope for improving prognosis in affected individuals.

References

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