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Attribution of causality in Stevens-Johnson syndrome/toxic epidermal necrolysis
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DOI：10.1016/j.jtos.2025.06.004.png)
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Abstract
En 中文
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an acute, severe immunobullous disorder of skin and mucous membranes that is most commonly induced by exposure to drugs. Causation of SJS/TEN is most often determined by the “algorithm of drug causality for epidermal necrolysis” (ALDEN) tool. However, concerns remain regarding the precision of ALDEN and causality assessment tools, potentially impacting ongoing studies attempting to link specific genotypes with specific drug classes as causes. To determine whether a standard of care exists in attribution of causation in SJS/TEN, we performed a narrative review of current concepts on causation in SJS/TEN, and available clinical and laboratory assessment tools for attributing causation. We found that current SJS/TEN causality attribution tools, including ALDEN, are somewhat limited by underlying assumptions. The utility of ex vivo tests proposed for determining causation in SJS/TEN, specifically the lymphocyte transformation test and cytokine stimulation assays, remain under investigation and are either not tractable for acute SJS/TEN or are not yet validated. In summary, a critical unmet need exists in the care of SJS/TEN patients, namely the difficulty in determining a precise cause in any specific individual. This shortfall limits the clinician's ability to discontinue only the causal agent in the acute phase, confounds studies of pathogenesis, and leaves affected patients in the chronic phase without knowing which drug or drug class is safe to use in the future. Further studies are needed to close this critical gap in the care of this devastating disease.
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