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AT-A-GLANCE

AT-A-GLANCE

  • Epidermal necrolysis is a rare life-threatening reaction mainly induced by medication.

  • Widespread apoptosis of keratinocytes is 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 often start on the upper trunk and spread to the limbs associated with mucous membrane involvement.

  • Histopathology shows full-thickness necrosis of epidermis associated with mild mononuclear cell infiltrate.

  • A dozen “high-risk” drugs account for half of cases.

  • More than 20% of cases remain idiopathic or may be caused by infection.

  • Early identification and withdrawal of suspect medication in drug-induced cases are essential for good patient outcomes.

  • Treatment consists mainly of supportive care, but recent evidence suggests a significant benefit of immunomodulating treatment with cyclosporine.

  • The death rate is high and increases with disease severity and age of the patient. The majority of survivors have long-lasting sequelae, needing systematic follow-up examinations.

INTRODUCTION

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis and mucosal epithelium (Table 44-1). In 1922, 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 Because SJS and TEN share clinical pattern, histopathologic findings, etiology, risk factors, and mechanisms, they are considered as severity variants of one disease entity that differs only in the extent of skin detachment related to the body surface area.3-5 Therefore, it seems more appropriate to use the designation epidermal (or epithelial) necrolysis for both, as proposed by Ruiz-Maldonado (acute disseminated epidermal necrosis)6 and Lyell (exanthematic necrolysis).7

Table 44-1Consensus Definition of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysisa

EPIDEMIOLOGY

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.8-10 Whereas incidences as high as 5 or 6 cases per million per year derive from medical databases not primarily designed for epidemiologic analysis of rare diseases,11 incidences of 1 to 2 cases per million per year were calculated using population-based prospective case registry data....

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