Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later the skin begins to blister and peel forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia, and multiple organ failure. The most common cause is certain medications such as lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics, and nevirapine. Other causes can include infections such as Mycoplasma pneumoniae and cytomegalovirus or the cause may remain unknown. Risk factors include HIV/AIDS and systemic lupus erythematosus. Diagnosis is based on a skin biopsy and involvement of more than 30% of the skin. TEN is a type of severe cutaneous adverse reactions (SCARs), together with SJS, a SJS/TEN, and drug reaction with eosinophilia and systemic symptoms. It is called SJS when less than 10% of the skin is involved and an intermediate form with 10 to 30% involvement. Erythema multiforme (EM) is generally considered a separate condition. Treatment typically takes place in hospital such as in a burn unit or intensive care unit. Efforts include stopping the cause, pain medication, and antihistamines. Antibiotics, intravenous immunoglobulins, and corticosteroids may also be used. Treatments do not typically change the course of the underlying disease. Together with SJS it affects 1 to 2 persons per million per year. It is more common in females than males. Typical onset is over the age of 40. Skin usually regrows over two to three weeks; however, recovery can take months and most are left with chronic problems.
Signs and symptoms
Prodrome TEN ultimately results in extensive skin involvement with redness, necrosis, and detachment of the top (epidermal) layer of the skin and mucosa. Before these severe findings develop, people often have a flu-like prodrome, with a cough, runny nose, fever, decreased appetite and malaise. A history of drug exposure exists on average 14 days (ranging from 1–4 weeks) prior to the onset of symptoms, but may result as early as 48 hours if it is a reexposure.
Skin findings Initial skin findings include red-purple, dusky, flat spots known as macules that start on the trunk and spread out from there. These skin lesions then transform into large blisters. The affected skin can then become necrotic or sag from the body and peel off in great swaths.
Mucosal findings Nearly all people with TEN have oral, eye and genital involvement as well. Painful crusts and erosions may develop on any mucosal surface. 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 can become swollen, crusted, and ulcerated, leading to potential blindness. The most common problem with the eyes is severe conjunctivitis.
Complications Those who survive the acute phase of TEN often develop long-term complications affecting the skin and eyes. Skin manifestations can include scarring, eruptive melanocytic nevi, vulvovaginal stenosis, and dyspareunia. The epithelium of the trachea, bronchi, or gastrointestinal tract may be involved in SJS and TEN. Ocular symptoms are the most common complication in TEN, experienced by 20–79% of those with TEN, even by those who do not experience immediate ocular manifestations. These can include dry eyes, photophobia, symblepharon, corneal scarring or xerosis, subconjunctival fibrosis, trichiasis, decreased visual acuity, and blindness.
Cause Drug reactions have been reported to cause 80–95% of TEN cases. The drugs most often implicated in TEN are:
antibiotics sulfonamides (sulfamethoxazole, sulfadiazine, sulfapyridine) beta-lactams (cephalosporins, penicillins, carbapenems) nonsteroidal anti-inflammatory drugs allopurinol antimetabolites (methotrexate) antiretroviral drugs (nevirapine) corticosteroids anxiolytics (chlormezanone) anticonvulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine, and valproic acid). TEN has also been reported to result from infection with Mycoplasma pneumoniae or dengue virus. Contrast agents used in imaging studies as well as transplantation of bone marrow or organs have also been linked to TEN development.
HIV HIV-positive individuals have 1000 times the risk of developing SJS/TEN compared to the general population. The reason for this increased risk is not clear.
Genetics Certain genetic factors are associated with increased risk of TEN. For example, certain HLA-types such as, HLA-B*1502, HLA-A*3101, HLA-B*5801, and HLA‐B*57:01 have been seen to be linked with TEN development when exposed to specific drugs.
Pathogenesis The immune system's role in the precise pathogenesis of TEN remains unclear. It appears that a certain type of immune cell (cytotoxic CD8+ T cell) is primarily responsible for keratinocyte death and subsequent skin detachment. Keratinocytes are the cells found lower in the epidermis and specialize in holding the surrounding skin cells together. It is theorized that CD8+ immune cells become overactive by stimulation from drugs or drug metabolites. CD8+ T cells then mediate keratinocyte cell death through release of a number of molecules, including perforin, granzyme B, and granulysin. Other agents, including tumor necrosis factor alpha and Fas ligand, also appear to be involved in TEN pathogenesis.
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