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Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum
Toxic epidermal necrolysis (TEN) is an acute and severe skin disease with clinical and histological features characterized by the destruction and detachment of the skin epithelium and mucous membranes.
ORPHA:95455Classification level: Disorder
Annual incidence is around 1/500,000. Females are more often affected than males.
Onset may occur at any age, but the risk increases after 40 years. Three subforms have been described according to the percentage of the body surface area affected: Stevens-Johnson syndrome (<10%; see this term), Lyell syndrome (>=30%; see this term) and an intermediate form (10-29%). The initial manifestations are nonspecific: a seemingly banal rash, fever, and a burning sensation involving the eyes, mouth and genitalia. The rash rapidly progresses to become vesicular and bullous on the face and body. The cutaneous vesicles aggregate and rupture under mild friction, revealing denuded red skin with seeping and pain. Mucous membrane lesions are present in 85 to 95% of patients with involvement, in order of frequency, of the oropharynx, eyes, genitalia and anus. Lesions are painful and lead to hypersalivation, feeding problems, photophobia, and burns following urination. High fever is a constant feature. Visceral manifestations are also frequent with hematological, respiratory and digestive involvement.
In two thirds of cases, TEN is triggered by a clearly identifiable drug allergy. A dozen high risk drugs have been identified: allopurinol, anti-infective sulphonamide agents, lamotrigine, nevirapine, carbamazepine, phenobarbital, phenytoin, and oxicam-derived nonsteroidal anti-inflammatory drugs. In rare cases, the disease is associated with infections (in particular, Mycoplasma pneumonia) or bone marrow transplantation. The remaining 25-30% of cases are classed as idiopathic, but some of these cases may be associated with failure to identify the causative drug. The clinical diagnosis should be confirmed by skin biopsy, which will reveal epidermal necrosis and the absence of antibody deposits.
The differential diagnosis should include chicken pox during the early stages of the disease, staphylococcal epidermolysis, staphylococcal scalded skin syndrome (associated with superficial skin peeling caused by a specific staphylococcal toxin and usually occurring in neonates), and, more rarely, autoimmune bullous diseases (excluded by examination of skin biopsies). In addition, the more limited forms of TEN are still often misdiagnosed as erythema multiforme major.
Management and treatment
Patients should be admitted to an intensive care or burns unit as soon as the diagnosis is suspected. The causative drug, together with any related compounds should be contraindicated for the patient and their close relatives (in case a genetic predisposition). No disease-modifying drugs have been shown be efficient in the treatment of TEN. The benefits of general corticotherapy and cyclosporine administration are still under evaluation. High-dose intravenous immunoglobulins are costly and appear to be of limited efficacy. Intensive symptomatic management is essential: a heated environment, analgesia, daily dressing changes, prevention of infections, and symptomatic intensive care measures (hydration, nutrition, and hyperbaric oxygen therapy).
Reepithelialization is rapid (2-3 weeks). However, the prognosis for patients with extensive forms of TEN is poor (mortality rate: 20-25%). Sequelae are reported in over 80% of surviving patients with ocular sequelae being the most problematic as they tend to be severe and progressive. Other sequelae (cutaneous, genital, buccal/dental or bronchial problems) are generally easier to detect and treat.