Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis are severe cutaneous adverse reactions that are of major concern because of high mortality rates. On the basis of data collected in the RegiSCAR study, the aim was to assess risk factors (including modalities of patient management) for mortality, regardless of the cause, up to 1 year after the reaction. Within this cohort, the mortality rate was 23% (95% confidence interval (CI) 19-27%) at 6 weeks and 34% (95% CI 30-39%) at 1 year. Severity of reaction was a risk factor for mortality only in the first 90 days after onset, whereas serious comorbidities and age influenced mortality beyond 90 days and up to 1 year after onset of reaction. The risk of death for patients with identified drug cause was borderline lower than for patients with a reaction of unknown cause (hazard ratio 0.66, 95% CI 0.45-0.96). The study could not provide conclusive evidence regarding patient management. This large-scale population-based follow-up study of such patients confirmed high in-hospital mortality and revealed a remarkable number of deaths after discharge, which could mainly be attributed to severe comorbidities and older age, whereas the impact of severity of reaction on the risk of death was limited to the first few weeks.

Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe.

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.

Evaluation of SCORTEN on a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis included in the RegiSCAR study.

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.

Toxic epidermal necrolysis in pregnancy: case report and review of the literature.

The authors report the case of a 29-year-old pregnant woman (2g1p) in the 16th week of gestation presenting with extensive toxic epidermal necrolysis (TEN). The cutaneous symptoms began at hands, feet, and in the mouth and developed during the course of 10 days to cover 75% of her TBSA, whereas total epidermolysis was present on more than 40% of her TBSA. Because of progressive swelling and bleeding of the oral mucosa, tracheal intubation was necessary to secure the airway of the patient. Critical care management required sedation, tracheotomy and artificial ventilation (14 days), prolonged fluid resuscitation, daily wound care, topical antiseptic and systemic antibiotic medication, hemostatic therapy and blood transfusion, hypercaloric nutrition, and frequent obstetric ultrasound evaluations. Reepithelialization began simultaneously with progressive epidermolysis and was completed after 35 days of conservative treatment. Because the patient experienced a swollen vulva and a stenotic birth channel, typical sequelae of TEN, a primary cesarean section was required after 40 weeks of gestation. The male infant showed neither signs of skin detachment nor sequelae caused by the prolonged therapy for the mother. A multidisciplinary approach and appropriate medical infrastructure are required to solve the challenge of TEN in pregnancy. In addition, the particular role of gestation in the pathophysiology of TEN needs to be explored further.

Neopterin and C-reactive protein in the course of Stevens-Johnson syndrome: report of a case.

We describe a patient originally suffering from a depressive syndrome who developed Stevens-Johnson syndrome after 12 days of treatment with lamotrigine. The clinical symptoms and the inflammation parameters neopterin and C-reactive protein were documented. Neopterin values showed a good correlation with the course of the disease, which, to the best of our knowledge, has not been reported previously. C-reactive protein followed the neopterin curve with a delay of 4 days. Since neopterin is a widely available parameter it should be considered as a routine measurement in this type of hyperergic reaction. It might help to identify the beginning, the maximum and the regression of the disease in order to support therapeutic decisions.