Toxic epidermal necrolysis

Overview
Toxic Epidermal Necrolysis (TEN), also known as Lyell's syndrome, is a life-threatening dermatological condition that is frequently induced by a reaction to medications. It is characterized by the detachment of the top layer of skin (the epidermis) from the lower layers of the skin (the dermis) all over the body.

There is broad agreement in the medical literature that TEN can be considered a more severe form of Stevens-Johnson syndrome and debate whether it falls on a spectrum of disease that includes erythema multiforme.

The incidence is between 0.4 and 1.2 cases per million each year.

Pathogenesis
Microscopically, TEN causes cell death throughout the epidermis. Keratinocytes, which are the cells found lower in the dermis, specialize in holding the skin cells together, undergo necrosis (uncontrolled cell death).

Etiology
Toxic epidermal necrolysis is a rare and usually severe adverse reaction to certain drugs. History of medication use exists in over 95% of patients with TEN. The drugs most often implicated in TEN are antibiotics such as sulfonamides; nonsteroidal anti-inflammatory drugs; allopurinol, antiretroviral drugs; and corticosteroids; and anticonvulsants such as phenobarbital, phenytoin, carbamazepine, and valproic acid. The condition might also result from immunizations, infection with agents such as Mycoplasma pneumoniae or the herpes virus; and transplants of bone marrow or organs.

Symptoms
TEN affects many parts of the body, but it most severely affects the mucous membranes, such as the mouth, eyes, and vagina. The severe findings of TEN are often preceded by 1 to 2 weeks of fever. These symptoms may mimic those of a common upper respiratory tract infection. When the rash appears it may be over large and varied parts of the body, and it is usually warm and appears red. In hours, the skin becomes painful and the epidermis can be easily peeled away from the underlying dermis. The mouth becomes blistered and eroded, making eating difficult and sometimes necessitating feeding through a nasogastric tube through the nose or a gastric tube directly into the stomach. The eyes are affected, becoming swollen, crusted, and ulcerated.

Diagnosis
Often, the diagnosis can be made clinically. Generally, if the clinical history is consistent with Stevens-Johnson syndrome, and the skin lesion covers greater than 30% of the body surface area, the diagnosis of TEN is appropriate. Sometimes, however, examination of affected tissue under the microscope may be needed to distinguish it between other entities such as staphylococcal scalded skin syndrome. Typical histological criteria of TEN include mild infiltrate of lymphocytes which may obscure the dermoepidermal junction and prominent cell death with basal vacuolar change and individual cell necrosis.

Treatment
First Line: early withdrawal of culprit drugs, early referral and management in burn units or intensive care units, supportive management, nutritional support

Second Line: Intravenous immunoglobulin (IVIG) - Uncontrolled trials showed promising effect of IVIG on treatment of TEN; a randomized control trial is needed in the future to determine the efficacy of IVIG in TEN.

Third Line: cyclosporin, cyclophosphamide, plasmapheresis, pentoxifylline, N-acetylcysteine, ulinastatin, infliximab, Granulocyte colony-stimulating factors (if TEN associated-leukopenia)

Systemic steroids are unlikely to offer any benefits.

Prognosis
The mortality for toxic epidermal necrolysis is 30-40 per cent. Loss of the skin leaves patients vulnerable to infections from fungi and bacteria, and can result in septicemia, the leading cause of death in the disease. Death is caused either by infection or by respiratory distress which is either due to pneumonia or damage to the linings of the airway. Microscopic analysis of tissue (especially the degree of dermal mononuclear inflammation and the degree of inflammation in general) can play a role in determining the prognosis of individual cases.