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Background: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe drug reactions associated with high mortality and multiple incapacitating sequelae. In the past 20 years, two large multinational case control studies, published in 1995 and 2008, had identified different degrees of drug association with SJS/TEN: 'strongly associated', 'associated', 'suspected' and 'not suspected' medications., Objective: The aim of this study was to check the adequacy of mention of risk of SJS/TEN in the drug dictionaries most widely used by physicians in five European countries., Study Design: In each country one expert investigator looked at the most widely used drug dictionary (2009 edition) for mentions of risk of SJS/TEN. This was done for a predefined list of medications with a different degree of risk. The presence and clarity or absence of warning was compared with available evidence provided by published results from case-control studies., Setting: The five countries participating in the RegiSCAR group: Austria, France, Germany, The Netherlands and the UK., Results: A total of 3,268 drug descriptions of medications for systemic use were analysed, including all brands of 14 'strongly associated' drugs, 5 'associated' drugs and 12 widely used drugs with no established association. Discrepancies were found by country, and between descriptions for different brands of the same generic. Among 522 descriptions of 14 'strongly associated' drugs, only 5 did not mention the risk. For the 1,013 descriptions of 'associated' drugs, 3 % did not mention the risk. One-third of 'not suspected' drugs contained a specific or less specific warning (e.g. bullous cutaneous eruption). Warnings for 'strongly associated' medications were often as imprecise as those for 'not suspected' drugs., Conclusion: Information on the risk of SJS/TEN in drug dictionaries needs improvement to enhance the quality of advice given by general physicians and to raise the understanding of risk by patients.

Background: Generalized bullous fixed drug eruption (GBFDE) is a rare cutaneous adverse reaction to drugs, and may resemble Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), but is usually considered less severe., Objectives: To compare the severity and mortality rate in cases of GBFDE and control cases of SJS or TEN of similar extent of skin detachment., Methods: This was a case-control analysis of 58 patients with GBFDE matched by age and extent of skin detachment to 170 control patients with a validated diagnosis of SJS or SJS/TEN overlap. Data for cases and controls were extracted from the EuroSCAR and RegiSCAR databases resulting from two population-based studies of severe cutaneous adverse reactions conducted in Europe. Preselected outcome criteria were death (primary), and fever, duration of hospitalization and transfer to an intensive care or burn unit (secondary)., Results: GBFDE affected mainly older patients (median age 78 years, interquartile range 68-84 years); 13 of 58 cases died (22%). The mortality rate was slightly but not significantly lower for patients with GBFDE than controls [28%, multivariate odds ratio 0·6 (95% confidence interval 0·30-1·4)]. Patients with GBFDE and controls did not differ in other preselected criteria for severity., Conclusions: Although our study featured limited statistical power, we were not able to confirm that GBFDE had better prognosis than SJS or SJS/TEN of similar disease extent in older patients. Severe cases of GBFDE deserve the attention and active management given to patients with SJS or TEN., (© 2013 The Authors. BJD © 2013 British Association of Dermatologists.)

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but extremely severe cutaneous adverse drug reactions in which drug-specific associations with HLA-B alleles were described., Objectives: To investigate genetic association at a genome-wide level on a large sample of SJS/TEN patients., Methods: We performed a genome wide association study on a sample of 424 European cases and 1,881 controls selected from a Reference Control Panel., Results: Six SNPs located in the HLA region showed significant evidence for association (OR range: 1.53-1.74). The haplotype formed by their risk allele was more associated with the disease than any of the single SNPs and was even much stronger in patients exposed to allopurinol (OR(allopurinol) = 7.77, 95%CI = [4.66; 12.98]). The associated haplotype is in linkage disequilibrium with the HLA-B*5801 allele known to be associated with allopurinol induced SJS/TEN in Asian populations., Conclusion: The involvement of genetic variants located in the HLA region in SJS/TEN is confirmed in European samples, but no other locus reaches genome-wide statistical significance in this sample that is also the largest one collected so far. If some loci outside HLA play a role in SJS/TEN, their effect is thus likely to be very small.

The purpose of this study was to evaluate the severity-of-illness score called SCORTEN with respect to its predictive ability and by using data obtained in the RegiSCAR study, the most comprehensive European registry of patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). For advanced comparisons, an auxiliary score (AS) was defined using data obtained in a previous study. Three hundred sixty-nine patients with SJS/TEN were included in RegiSCAR between 2003 and 2005. The data needed for calculation of SCORTEN were available for 45% of patients. The score revealed a moderate predictive ability with a slight underestimation of the total number of in-hospital deaths by 11%, an area under the receiver operating characteristic curve of 0.75, and a Brier score of 0.14. Problems could be seen by analyzing subgroups such as patients with TEN. The AS was better calibrated but discriminated worse (area under the receiver operating characteristic curve: 0.72; Brier score: 0.14). With the help of a refined score derived from SCORTEN and AS, potential for a possible improvement could be demonstrated. The authors were able to show that the predictive ability of SCORTEN is acceptable. Although improvement might be possible, SCORTEN remains the tool of choice, whereas AS might be an alternative in retrospective settings with missing laboratory data.

Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case-control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case-control analysis had described as "probably not associated" and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case-control analysis results, can be considered a reference tool in SJS/TEN.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions., Objectives: We sought to update knowledge on the causes of SJS or TEN with a focus on the rate of allopurinol-associated cases and to identify risk factors for allopurinol-associated SJS or TEN., Methods: We conducted a multinational case-control study., Results: In all, 379 patients with severe cutaneous adverse reactions validated as SJS or TEN and 1505 matched hospitalized control subjects were enrolled. Allopurinol was the drug most frequently associated with SJS or TEN, with 66 exposed patients (17.4%) and 28 exposed control subjects (1.9%) (adjusted odds ratio = 18, 95% confidence interval: 11-32). Allopurinol use was greater than in a previous case-control European study. Daily doses equal to or greater than 200 mg were associated with a higher risk (adjusted odds ratio = 36, 95% confidence interval: 17-76) than lower doses (adjusted odds ratio = 3.0, 95% confidence interval: 1.1-8.4). The risk was restricted to short-term use (