OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe blistering skin diseases, which are mainly caused by drugs. The two idiosyncratic conditions are distinguished on the basis of the degree of blistering, possibly representing diseases at different ends of the same spectrum. A genetic predisposition has been postulated. METHOD: We have retrospectively identified a heterogeneous group of patients with SJS and TEN (n = 73 cases, 141 matched controls) induced by a number of marketed drugs and evaluated effector candidate genetic predisposition. We have used a multivariate genetic analysis method for the first time to handle the heterogeneity of clinical presentation, drug etiology, ethnicity and gender in these adverse events. RESULTS: Our results show that predisposition varied according to ethnicity. There was a correlation for SJS with HLA-B*44, DRB1*07 and with the MHC ancestral 57.1 haplotype (and its constituents) in subjects who self-reported as Caucasians, which did not differ with gender. The HLA-DRB and -DRQ genetic predisposition to SJS seemed to be distinct from that of TEN, but further work is needed for both conditions to identify the causal variants. No conclusion concerning correlations with different drugs could be made because of small numbers in each drug group. CONCLUSION: This study stresses the importance of accurate clinical phenotyping, exemplifies a novel analysis method to dissect complicated samples and calls for collaborative prospective studies.
OBJECTIVE:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe blistering skin diseases, which are mainly caused by drugs. The two idiosyncratic conditions are distinguished on the basis of the degree of blistering, possibly representing diseases at different ends of the same spectrum. A genetic predisposition has been postulated. METHOD: We have retrospectively identified a heterogeneous group of patients with SJS and TEN (n = 73 cases, 141 matched controls) induced by a number of marketed drugs and evaluated effector candidate genetic predisposition. We have used a multivariate genetic analysis method for the first time to handle the heterogeneity of clinical presentation, drug etiology, ethnicity and gender in these adverse events. RESULTS: Our results show that predisposition varied according to ethnicity. There was a correlation for SJS with HLA-B*44, DRB1*07 and with the MHC ancestral 57.1 haplotype (and its constituents) in subjects who self-reported as Caucasians, which did not differ with gender. The HLA-DRB and -DRQ genetic predisposition to SJS seemed to be distinct from that of TEN, but further work is needed for both conditions to identify the causal variants. No conclusion concerning correlations with different drugs could be made because of small numbers in each drug group. CONCLUSION: This study stresses the importance of accurate clinical phenotyping, exemplifies a novel analysis method to dissect complicated samples and calls for collaborative prospective studies.
Authors: Krystyna Romańska-Gocka; Jacek Gocki; Waldemar Placek; Barbara Zegarska; Paweł Krause Journal: Arch Med Sci Date: 2010-03-09 Impact factor: 3.318
Authors: Paola Nicoletti; Sarah Barrett; Laurence McEvoy; Ann K Daly; Guruprasad Aithal; M Isabel Lucena; Raul J Andrade; Mia Wadelius; Pär Hallberg; Camilla Stephens; Einar S Bjornsson; Peter Friedmann; Kati Kainu; Tarja Laitinen; Anthony Marson; Mariam Molokhia; Elizabeth Phillips; Werner Pichler; Antonino Romano; Neil Shear; Graeme Sills; Luciana K Tanno; Ashley Swale; Aris Floratos; Yufeng Shen; Matthew R Nelson; Paul B Watkins; Mark J Daly; Andrew P Morris; Ana Alfirevic; Munir Pirmohamed Journal: Clin Pharmacol Ther Date: 2019-07-03 Impact factor: 6.875