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Drugs can induce severe skin reactions that differ in clinical presentation, prognosis, and therapy. The spectrum of these reactions not only includes bullous reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and generalized bullous fixed drug eruption (GBFDE) but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). If AGEP or DRESS is suspected, the diagnosis should be confirmed by thorough clinical examination, a skin biopsy, and specific laboratory tests. Crucial for the patient's prognosis, the causative agent should be rapidly identified and discontinued. It is therefore important to know the most frequent triggers of severe drug reactions, some of which may induce various reaction patterns. Depending on the clinical diagnosis, symptomatic and adequate supportive therapy, as well as systemic immunomodulatory treatments are used. The prognosis in SJS/TEN is often poor and depends on the patient's age and underlying conditions as well as the extent of skin detachment. The prognosis of GBFDE is somewhat better, but recurrences may lead to more severe disease manifestations. In DRESS, protracted and recurrent courses have been described, whereas AGEP usually resolves without problems.

Summary The spectrum of severe drug-induced skin reactions includes not only Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) but also generalized bullous fixed drug eruption (GBFDE), acute generalized exanthematous pustulosis (AGEP) and hypersensitivity syndrome (HSS), also called drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions differ in clinical presentation as well as prognosis, causative agents and therapy. Therefore, the appropriate diagnostic measures should be undertaken rapidly, in order to prove the diagnosis. In addition to a thorough clinical examination, a skin biopsy should be taken and specific laboratory investigations should be done if AGEP or HSS/DRESS is suspected. Since these reactions are drug-induced, the causative agent should be rapidly identified and withdrawn. Besides adequate supportive therapy, systemic immunomodulatory treatments may be considered. Despite intensive care management, the prognosis in SJS and TEN is often poor and influenced by the amount of skin detachment as well as the age of the patients and the pre-existing underlying conditions. Severe sequelae may develop in survivors and affect especially mucosal sites. The prognosis of GBFDE is better but recurrent events may lead to more severe involvement. In HSS/DRESS sequelae have been also described as well as long lasting and recurrent courses, whereas AGEP usually heals without problems.