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Stevens–Johnson syndrome and toxic epidermal necrolysis represent a spectrum of severe cutaneous adverse reactions that carry the potential for severe, long-term adverse effects, including death. Although medications are most commonly implicated in the development of these diseases, other factors, including infection and genetics, play a role. Management is generally supportive in nature and includes maintenance of the patient's airway, breathing, and circulation. Special disease considerations include the use of skin barrier management, unique infection prevention measures, and systemic immunomodulatory therapies.