Toxic epidermal necrolysis (Lyell's disease)

Abstract 

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions, characterized by a low incidence but high mortality, initially described as separate entities, but today considered variants of the same pathologic process and differing only for severity.

The majority of cases appear to be related to idiosyncratic drug reactions. The drugs most commonly involved are: antibiotics such as sulfonamides, β-lactam, tetracyclines and quinolones; anticonvulsants such as phenytoin, phenobarbital and carbamazapine; antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol.

There is common agreement to consider TEN as the manifestation of a disregulated immune reaction against epithelial cells. During the first stages of TEN, apoptosis mediates keratinocyte death and the pivotal role of Fas–FasL pathway activation during TEN is undoubted. T cell cytotoxicity, demonstrated during TEN, has been shown to be mediated by the perforin–granzyme pathway. It seems, also, clear that a peculiar cytokine pattern plays an important role in TEN pathogenesis.

The cutaneous findings result in an acute macular erythematous rash with bullae. These lesions rapidly exhibit Nikolsky's sign and a separation of large sheets of epidermis from the dermis and a subsequent localised shedding develops rapidly, which can become very extensive.

When feasible, admission in burn or intensive care unit, positioning the patients in air-fluidised beds, is universally considered crucial in TEN treatment.

The prompt withdrawal of the suspected drug, fluid and electrolyte replacement and topical wound care are the first line of therapy.

The use of corticosteroids has been abandoned and the role of immunosuppressants, despite some success, is not well defined and is not considered as a standard. A trial comparing thalidomide versus placebo in TEN patients was suspended because mortality rate increased in the treated group. Infliximab, a chimeric monoclonal antibody to TNF-α, has been administered to a patient, in single infusion, with a favourable outcome. Plasmapheresis is reported to lead to some success in TEN treatment, with improvement of clinical conditions and high percentage of survival.

Different authors reported good results in terms of decreasing mortality and morbidity or improving clinical conditions of the use of human intravenous immunoglobulins (IVIGs). Regardless, the true utility of this treatment remains controversial.

In 2005, the authors (ML and RC), dealing with a number of severe TEN cases, proposed a new protocol based on the combination of these last two techniques reporting their preliminary results in the treatment of severe TEN patients.

Keywords: Lyell's disease, Plasmapheresis, IVIG, Drug reactions, SCORTEN, Stevens–Johnson's syndrome