CME Dermatology

Abstract

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, potentially life-threatening medical emergencies, characterised by widespread epidermal loss with mucous membrane involvement. Most cases are attributable to drugs (Table 1), so knowledge of these conditions is essential for all physicians. Rarely, infections (eg Mycoplasma pneumoniae) may be responsible. The annual incidence of TEN and SJS is 0.4-1.2 and 1.2-6 cases per million per year, respectively. 1 Women are more frequently affected (1.5:1) and the incidence increases with age. 2 Individuals at particular risk include 'slow acetylators' , patients treated for brain neoplasms or head injury and immunocompromised patients. The risk of developing TEN is a thousand times higher in patients with HIV and AIDS than in the normal population. 3 Possible explanations include the HIV infection itself, the increased number of drugs these patients receive and the altered ratio between CD4 + and CD8 + T lymphocytes. 4 This article presents an overview of the aetiology, pathogenesis and clinical features of TEN and SJS and discusses the principles of management and the role of potential disease-modifying therapies. Pathogenesis The precise molecular basis of TEN and SJS still remains to be fully elucidated. It appears that TEN patients, who have an increased incidence of the haplotype HLA-B12, 5 demonstrate an inability to detoxify intermediate reactive drug metabolites. An immune response is then mounted against the antigenic complexes formed by the interaction of these metabolites and host tissues. 6,7 There is also compelling evidence that the end-point of TEN and SJS (ie epidermal necrolysis) is due to widespread apoptosis of keratinocytes. 8 Cytokines such as inter-leukin-6, tumour necrosis factor alpha and the CD95 system (Fas ligand and Fas receptor) appear to play a role in the induction of this apoptosis 9-11 and consequently have become targets for possible therapeutic interventions in TEN.