Epidermal Necrolysis at a Glance
- Rare and life-threatening reaction, mainly drug induced.
- Widespread apoptosis of keratinocytes provoked by the activation of a cell-mediated cytotoxic reaction and amplified by cytokines, mainly granulysin.
- Confluent purpuric and erythematous macules evolving to flaccid blisters and epidermal detachment predominating on the trunk and upper limbs and associated with mucous membrane involvement.
- Pathologic analysis shows full-thickness necrosis of epidermis associated with mild mononuclear cell infiltrate.
- A dozen “high-risk” drugs account for one half of cases.
- Up to 20% of cases remain idiopathic.
- Early identification and withdrawal of suspect drugs are essential for good patient outcome.
- Treatment is mainly symptomatic.
- Sequelae are nearly constant, needing systematic follow-up examinations.
Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are acute life-threatening mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis. Stevens and Johnson first reported two cases of disseminated cutaneous eruptions associated with an erosive stomatitis and severe ocular involvement.1 In 1956, Lyell described patients with epidermal loss secondary to necrosis and introduced the term toxic epidermal necrolysis.2 Both SJS and TEN are characterized by skin and mucous membrane involvement. Because of the similarities in clinical and histopathologic findings, risk factors, drug causality, and mechanisms, these two conditions are now considered severity variants of an identical process that differs only in the final extent of body surface involved.3–5 Therefore, it is better to use the designation epidermal necrolysis for both, as proposed by Ruiz-Maldonado (acute disseminated epidermal necrosis)6 and Lyell (exanthematic necrolysis).7
Epidermal necrolysis (EN) is rare. The overall incidence of SJS and TEN was estimated at 1 to 6 cases per million person-years and 0.4 to 1.2 cases per million person-years, respectively.8,9 EN can occur at any age, with the risk increasing with age after the fourth decade, and more frequently affects women, showing a sex ratio of 0.6. Patients infected with human immunodeficiency virus and to a lesser degree patients with collagen vascular disease and cancer are at increased risk.10–12 The overall mortality associated with EN is 20% to 25%, varying from 5% to 12% for SJS to more than 30% for TEN. Increasing age, significant comorbidity, and greater extent of skin involvement correlate with poor prognosis. In the United States, evaluation of death certificates suggested a seven time higher risk of dying from EN among blacks than whites.13
A prognosis score (SCORTEN) has been constructed for EN,14 and its usefulness has been confirmed by several teams.15–18 (See Table 40-1.)
Table 40-1 SCORTEN: A Prognostic Scoring System for Patients with Epidermal Necrolysis ||Download (.pdf)
Table 40-1 SCORTEN: A Prognostic Scoring System for Patients with Epidermal Necrolysis
- Heart rate >120 beats/minute
- Cancer or hematologic malignancy
- Body surface area involved >10%