Epidemiology of drug-induced severe skin reactions

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, sometimes life-threatening skin reactions that are often drug-induced. Unfortunately, the definitions and nomenclature of these severe skin reactions have been confusing, and thus various publications on this issue can hardly be compared. After several attempts have been made to clarify this situation, a consensus definition published in 1993 suggests the differentiation between erythema exsudativum multiforme majus (EEMM) and SJS, as well as an overlap group of SJS and TEN, whereas TEN with maculae is the most severe type of skin reaction with more than 30% of skin detachment related to the body surface area (BSA). This classification was applied to cases of severe skin reactions in several large studies that have been undertaken within the last few years and published recently. The incidence of SJS, SJS/TEN overlap and TEN has been estimated to be approximately 1.89 cases per one million people per year. Although SJS and TEN occur very rarely, a mortality rate of more than 40% can be calculated for patients suffering from TEN. One may conclude that mortality increases with age and the amount of skin detachment related to the BSA. A number of drugs have been reported to induce severe skin reactions, eg, anti-infective sulfonamides, antibiotics, anticonvulsants and nonsteroidal anti-inflammatory drugs. For risk evaluation for certain drugs or drug groups population-based data as ascertained by the German registry of severe skin reactions, and prescription data in defined daily doses can be used. In addition, risk evaluation is possible by performing a case-control study as it has been undertaken within different European countries. As long as the pathogenesis of drug-induced severe skin reactions is not known, and specific screening methods to identify susceptible individuals do not exist, the epidemiological approach will remain the only possibility for risk estimation.